PatientID: None

KindredID: 11

Case: M, 15Y0M, Korean

DiseaseAssertion: VHL

FamilyInfo: His father had the same mutation and presented with hemangioblastoma, renal cyst, retinal capillary hemangioma, and renal cell carcinoma. The grandmother and aunt were also suspected to have VHL mutations, but their DNA was not evaluated.

CohortInfo: Thirteen unrelated patients with germline VHL mutations who were diagnosed with VHL disease were evaluated.

CasePresentingHPOs: HP:0010797 (hemangioblastoma)

CaseHPOFreeText: The patient developed a hemangioblastoma at age 15.

CaseNotHPOs: HP:0001732, HP:0002666, HP:0000107, HP:0009711, HP:0005584 (abnormality of the pancreas, pheochromocytoma, renal cyst, retinal capillary hemangioma, renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R167Q (c.500G>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVar: 2216 https://www.ncbi.nlm.nih.gov/clinvar/variation/2216/

CAID: N/A

gnomAD: 0.000003977 https://gnomad.broadinstitute.org/variant/3-10191507-G-A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: R167Q (c.500G>A)

MultipleGeneVariants: N/A

GroupID: 9

DiseaseAssertion: VHL

Group size: 8

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

Group Info: Retrospective analysis of a longitudinal cohort of 21 VHL germline mutation carriers and retinal haemangioblastomas. All patients were categorized in two genotypic categories: missense mutations and truncating mutations. From this family, eight individuals were suspected of VHL disease. 5/8 individuals developed RH, while 3/8 did not.

GroupPresentingHPOs: HP:0009711 (retinal capillary hemangioma)

GroupHPOFreeText: Five patients presented with retinal capillary hemangioma.

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Table S1

Variant: p.L159Es*15 (c.473dup)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: CA432423097, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.473dup

gnomAD: N/A

VariantEvidence: Chr3(GRCh37): g.10191480dup

MutationType: duplication; plus_1_frameshift_variant

CivicName: L159Es*15 (c.473dup)

MultipleGeneVariants: N/A

PatientID: 20

KindredID: 5

Case: M, 15Y0M, Spanish

DiseaseAssertion: VHL

FamilyInfo: The patient had first-degree familial antecedents.

CohortInfo: 36 pediatric patients with pheochromocytomas and/or parangangliomas.

CasePresentingHPOs: HP:0002666 (pheochromocytoma)

CaseHPOFreeText: The patient had a benign bilateral pheochromocytoma at age 15.

CaseNotHPOs: N/A

CaseNotHPOFreeText: The patient did not have any other tumours.

CasePreviousTesting: RET, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX

PreviouslyPublished: Yes source unknown.

SupplementalData: N/A

Variant: p.R167Q (c.500G>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVar: 2216 https://www.ncbi.nlm.nih.gov/clinvar/variation/2216/

CAID: N/A

gnomAD: 0.000003977 https://gnomad.broadinstitute.org/variant/3-10191507-G-A

VariantEvidence:N/A

MutationType: missense_variant;transition

CivicName: R167Q (c.500 G >A)

MultipleGeneVariants: N/A

PatientID: II

KindredID: 5

Case: Sex Unknown, 20Y0M, Danish

DiseaseAssertion: VHL

FamilyInfo: 2 family members with the same VHL variant. Patient 5-I presented with retinal hemangioblastoma (17Y). Patient 5-III presented with retinal hemangioblastoma (12Y), pancreatic cysts (12Y), CNS hemangioblastoma (15Y) and kidney disease (12Y).

CasePresentingHPOs: HP:0009711; HP:0010797; HP:0001737 (Retinal capillary hemangioma, Hemangioblastoma, Pancreatic cysts)

CaseHPOFreeText: Diagnosed with VHL at age 3Y. Presented with 13 CNS hemangioblastomas (11Y, 13Y, 15Y and 17Y), retinal hemangioblastoma (13Y) and 2 pancreatic cysts (16Y). Age at the end of study: 20Y.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Q145* (c.433C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 625249, https://www.ncbi.nlm.nih.gov/clinvar/variation/625249/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition; stop_gained

CivicName: Q145* (c.433C>T)

MultipleGeneVariants: N/A

PatientID: III

KindredID: 15

Case: Sex Unknown, 60Y0M, Danish

DiseaseAssertion: VHL

FamilyInfo: 2 other family members presented with the same VHL variant. Patient 15-II presented with 2 pheochromocytoma (8Y) 2 CNS hb (12Y and 13Y) and 2 retinal hemangioblastomas (8Y, 12Y). Patient 15-I was asymptomatic.

CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

CaseHPOFreeText: Diagnosed with VHL at age 15Y. Presented with 2 pheochromocytoma (15Y). Age at the end of study: 60Y.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.V166F (c.496G>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 2224, https://www.ncbi.nlm.nih.gov/clinvar/variation/2224/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: V166F (c.496G>T)

MultipleGeneVariants: N/A

PatientID: I

KindredID: 8

Case: Sex Unknown, 35Y0M, Danish

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0009711; HP:0010797 (Retinal capillary hemangioma, Hemangioblastoma)

CaseHPOFreeText: Diagnosed with VHL at age 15Y. Presented with 6 CNS hemangioblastomas (15Y) and 2 retinal hemangioblastomas (15Y). Age at the end of study: 15Y.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L118P (c.353T>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 428807, https://www.ncbi.nlm.nih.gov/clinvar/variation/428807/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: L118P (c.353T>C)

MultipleGeneVariants: Germline, VHL, c.319C>T (p.R107C)

PatientID: II-1

KindredID: Family C

Case: M, 45Y0M, Ethnicity unknown

DiseaseAssertion: VHL

FamilyInfo: Only this one member was studied at have the L198P mutation, however the asymptomatic father of patient C II-1 was also a carrier of the same polymorphism (c.74C>T, p.P25L).

CasePresentingHPOs: HP:0006748; HP:0030405; HP:0009711 (Adrenal pheochromocytoma; pancreatic neuroendocrine tumour; retinal capillary hemangioma)

CaseHPOFreeText: At the age of 15, patient had pancreatic tumor (malignant pancreatic neuroendocrine tumor). At the age of 16, MRI revealed suprarenal tumor masses bilaterally (pheochromocytomas in the adrenal glands), as well as optic nerve hemangioblastomas of the right eye. At the age of 25, he shows no signs of metastases or new VHL-associated tumors, but since the age of 23, he has been suffering from HLAB27-positive ankylosing spondylitis.

CaseNotHPOs: HP:0005584; HP:0010797 (renal cell carcinoma; hemangioblastoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P25L (c.74C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 93330 https://www.ncbi.nlm.nih.gov/clinvar/variation/93330/

CAID: N/A

gnomAD: 0.002988 https://gnomad.broadinstitute.org/variant/3-10183605-C-T

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: L198P (c.593T>C) AND P25L (c.74C>T)

MultipleGeneVariants: Germline, VHL, c.593T>C (p.Leu198Pro)

PatientID: None

KindredID: 8

Case: M, 15Y0M, Ethnicity unknown

DiseaseAssertion: assumed VHL

FamilyInfo: Familial/syndromic (FS) association

CasePresentingHPOs: HP:0002666; HP:0002668; HP:0009711 (Pheochromocytoma; paraganglioma; retinal capillary hemangioma)

CaseHPOFreeText: Benign sympathetic Paraganglioma at age 12Y0M and unilateral pheochromocytoma at age 15Y0M; as well as retinal angioma (age unclear)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: SDHB,SDHC, SDHD, and exons 10, 11, 13, 14, 15 and 16 of RET proto-oncogene

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Y98S (c.293A>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 219160 https://www.ncbi.nlm.nih.gov/clinvar/variation/219160/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: Y98S (c.293A>C)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 1

Case: M, 15Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: None

CasePresentingHPOs: HP:0030393 (Endolymphatic sac tumor)

CaseHPOFreeText: The patient had isolated left-sided hearing loss for more than 3 months. MRI showed a highly enhancing mass in the left temporal bone in the region of the jugular foramen, that measured 3.4 × 2.3 × 3.3 cm and exhibited a salt and pepper pattern in some areas. Definite histology confirmed ELST, and because a radical resection could not be guaranteed due to the highly infiltrative growth of the tumor, postoperative stereotactic radiation was initiated. The patient also had angiomatous lesions of the nasal and pharyngeal mucosa.

CaseNotHPOs: N/A

CaseNotHPOFreeText: The patient was screened for other VHL-associated tumors by fundoscopy and whole body positron-emission tomography-computed tomography, which did not show any pathological findings.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.N78S (c.233A>G)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 93326 https://www.ncbi.nlm.nih.gov/clinvar/variation/93326/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: N78S (c.233A>G)

MultipleGeneVariants: N/A

PatientID: 11

KindredID: 4

Case: M, 27Y0M, Indian

DiseaseAssertion: VHL

FamilyInfo: 2 other family members (relation unclear) presented with the same variant. Patient 9 (Gen 2) of these presented with unilateral pheochromocytoma and PNET. Patient 10 (Gen 1) presented with bilateral pheochromocytoma and sympathetic paraganglioma and PNET.

CohortInfo: This retrospective study was conducted at Department of Endocrinology of a tertiary care health centre in Western India. Patients presented to our institute between 2008 and 2016 were included in the study. During the study period a total of 33 patients were suspected to have VHL syndrome based on clinical features among whom 31 patients were found to have mutation in VHL gene. All patients are of Asian Indian descent.

CasePresentingHPOs: HP:0002666; HP:0002668; HP:0030405; HP:0009711; HP:0010797 (Pheochromocytoma, Paraganglioma, Pancreatic endocrine tumor, Retinal capillary hemangioma, Hemangioblastoma)

CaseHPOFreeText: Bilateral pheochromocytoma and sympathetic paraganglioma. Metastasis found at age 27. Age of onset for pheochromocytoma and paragangliomas is stated as 12Y and 15Y but it is not clear which age pertains to which phenotype.

CaseNotHPOs: HP:0001737; HP:0005584 (Pancreatic cysts, Renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Y98S (c.293A>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 219160, https://www.ncbi.nlm.nih.gov/clinvar/variation/219160/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: Y98S (c.293A>C)

MultipleGeneVariants: N/A

PatientID: 5299

KindredID: 235

Case: Sex Unknown, Age Unknown, French

DiseaseAssertion: VHL

FamilyInfo: N/A

CohortInfo: Families were recruited from the French VHL Registry. Enrolment in the study required identification of the germline VHL mutation (currently 85% of the families included in the French VHL Registry) and available data regarding renal phenotype. A total of 126 families fulfilled these criteria.

CasePresentingHPOs: HP:0009726 (Renal neoplasm)

CaseHPOFreeText: Mild renal disease (simple renal cyst, multicystic kidney[s], small lesion [less than 10 mm in size] of unknown significance, or small solid tumor without indication for surgical removal [less than 30 mm in size]). Individual RCC phenotype is noted as negative.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: Paper states that this family is previously reported in PMID 12202531 and/or 9829912, where 1 and 1 individuals respectively with an equivalent mutation (i.e. 473insT) are reported. It is unclear if one or both of these previously reported groups are the same as the current family.

SupplementalData: Phenotype and genotype information can be found in Supplementary Table S1.

Variant: p.K159Efs*15 (c.473dup)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA432423097, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.473dup

gnomAD: N/A

VariantEvidence: N/A

MutationType: duplication; plus_1_frameshift_variant

CivicName: K159Efs*15 (c.473dup)

MultipleGeneVariants: N/A

PatientID: IV-6

KindredID: 2

Case: F, 23Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Her 48Y father (Patient III-4) presented with hematuria at age 39Y and was found to have clear-cell renal-cell carcinoma, renal cysts, pancreatic cysts, and multiple hemangioblastomas of the cerebellum and lower brainstem. Her father was found to have mosaic VHL disease and the NM_000551.3:c.227_229del mutation the patient carried in approximately one of seven peripheral blood lymphocytes. The patient’s mother was unaffected. Of the patient’s three sisters and two brothers, one underwent clinical examination and two underwent genetic testing of unclear nature, and were found to be unaffected. The remaining two siblings were not evaluated.

CasePresentingHPOs: HP:0009713; HP:0001737; HP:0000107; HP:0000077; HP:0009711 (Spinal hemangioblastoma, pancreatic cyst, renal cyst, renal lesion, retinal hemangioma)

CaseHPOFreeText: The 23Y female patient was diagnosed with VHL disease at age 15 years, when she developed symptoms caused by spinal cord hemangioblastomas. At age 20 years, she was diagnosed with multiple cystic lesions in the right kidney, a solid lesion of the left kidney, multiple pancreatic cysts, and a small peripheral retinal angioma.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.F76del(c.226_228delTTC)

LegacyVariant: p.F76del(c.439_441delTTC)

ClinVarID: N/A

CAID: CA357012

gnomAD: N/A

VariantEvidence: N/A

MutationType: inframe_deletion

CivicName: F76del(c.226_228delTTC)

MultipleGeneVariants: N/A

PatientID: I

KindredID: 10

Case: Sex Unknown, 37Y0M, Danish

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0001737, HP:0009711, HP:0009715 (pancreatic cysts, retinal capillary hemangioma, Papillary cystadenoma of the epididymis)

CaseHPOFreeText: The patient was diagnosed with VHL at age 15 and presented with two pheochromocytomas. At age 17, the patient presented with a retinal capillary hemangioma and an epididymal cystadenoma.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 19863552, 25834951, 27966541, 27539272

SupplementalData: N/A

Variant: p.R113* (c.337C>T)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 220414 https://www.ncbi.nlm.nih.gov/clinvar/variation/220414/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType:stop_gained

CivicName: R113* (c.337C>T)

MultipleGeneVariants: N/A

PatientID: I

KindredID: 8

Case: Sex Unknown, 35Y0M, Danish

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0009711; HP:0010797 (Retinal capillary hemangioma, Hemangioblastoma)

CaseHPOFreeText: Diagnosed with VHL at age 15Y. Presented with 6 CNS hemangioblastomas (15Y) and 2 retinal hemangioblastomas (15Y). Age at the end of study: 15Y.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R107C (c.319C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351751195, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.319C%3ET

gnomAD: 0.000004522, https://gnomad.broadinstitute.org/variant/3-10183850-C-T?dataset=gnomad_r2_1

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: R107C (c.319C>T)

MultipleGeneVariants: Germline, VHL, c.353T>C (p.L118P)

PatientID: N/A (case)

KindredID: 1

Case: M, 18Y0M, Indian (South Asian)

DiseaseAssertion: assumed VHL

FamilyInfo: No positive family history, although his relatives have been advised to get mutation screening.

CasePresentingHPOs: HP:0006748; HP:0100653 (Adrenal pheochromocytoma; Optic neuritis)

CaseHPOFreeText: At 15Y (in 2017), male presented with history of acute bilateral vision loss, history of headaches, had bilateral disc edema - visual acuity of 6/36 both eyes (BE). A CT of his abdomen revealed bilateral pheochromocytoma, where he had an adrenalectomy.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R161Q (c.482G>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 182983, https://www.ncbi.nlm.nih.gov/clinvar/variation/182983/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: R161Q (c.482G>A)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 386

Case: M, 15Y0M, Polish

DiseaseAssertion: Pheochromocytoma

FamilyInfo: One of the patient’s brothers carried the mutation and presented with bilateral pheochromocytoma at 11Y. The patient’s mother also carried the mutation and presented with bilateral pheochromocytoma at 41Y.

CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

CaseHPOFreeText: The patient presented with unilateral pheochromocytoma at 15Y.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R167W(c.499C>T)

LegacyVariant: p.R238W(c.712C>T)

ClinVarID: 2218, http://www.ncbi.nlm.nih.gov/clinvar/variation/2218

gnomAD: 3:10191506 C / T, http://gnomad.broadinstitute.org/variant/3-10191506-C-T

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: R167W(c.499C>T)

MultipleGeneVariants: N/A

PatientID: II-1

KindredID: Family C

Case: M, 45Y0M, Ethnicity unknown

DiseaseAssertion: VHL

FamilyInfo: Only this one member was studied. This mutation was said to be a de novo, although no more inforation provided. However the asymptomatic father of patient was also a carrier of the same polymorphism (c.74C>T, p.P25L).

CasePresentingHPOs: HP:0006748; HP:0030405; HP:0009711 (Adrenal pheochromocytoma; pancreatic neuroendocrine tumour; retinal capillary hemangioma)

CaseHPOFreeText: At the age of 15, patient had pancreatic tumor (malignant pancreatic neuroendocrine tumor). At the age of 16, MRI revealed suprarenal tumor masses bilaterally (pheochromocytomas in the adrenal glands), as well as optic nerve hemangioblastomas of the right eye. At the age of 25, he shows no signs of metastases or new VHL-associated tumors, but since the age of 23, he has been suffering from HLAB27-positive ankylosing spondylitis.

CaseNotHPOs: HP:0005584; HP:0010797 (renal cell carcinoma; hemangioblastoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L198P (c.593T>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223235 https://www.ncbi.nlm.nih.gov/clinvar/variation/223235/

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: L198P (c.593T>C) AND P25L (c.74C>T)

MultipleGeneVariants: Germline, VHL, c.74C>T (p.Pro25Leu)

PatientID: II.1

KindredID: F1

Case: M, 15Y0M, Ethnicity Unknown

DiseaseAssertion: Polycythemia

FamilyInfo: N/A

CasePresentingHPOs: HP:0001901 (Polycythemia)

CaseHPOFreeText: Diagnosed with erythrocytosis (Polycythemia) and kidney ischemic infarct at age 15 (DOB: 1991).

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: c.340+770T>C

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 816685, https://www.ncbi.nlm.nih.gov/clinvar/variation/816685/

CAID: N/A

gnomAD: N/A

VariantEvidence: Variants are heterozygous.

MutationType: missense_variant;transition; splice_site_variant

CivicName: D143= (c.429C>T) and c.340+770T>C

MultipleGeneVariants: Germline, VHL, c.429C>T (p.Asp143Asp)

PatientID: 280

KindredID: 110

Case: M, 22Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: The proband, patient 280, presented with a CNS hemangioblastoma at age 16, a retinal angioma at age 15, and multiple pancreatic cysts/tumors at age 22. Their father presented with a CNS hemangioblastoma at age 25, and retinal angioma at age 29.

CasePresentingHPOs: HP:0010797; HP:0001737; HP:0001732; HP:0009711 (Hemangioblastoma, Pancreatic cysts, Abnormality of the pancreas, Retinal capillary hemangioma)

CaseHPOFreeText: The proband, patient 280, presented with a CNS hemangioblastoma at age 16, a retinal angioma at age 15, and multiple pancreatic cysts/tumors at age 22.

CaseNotHPOs: HP:0002666; HP:0005584 (Pheochromocytoma, Renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: This cohort was also published in a later paper by Wang et al., 2018 (PMID: 29330336).

SupplementalData: Patient and family genotype-phenotype information is listed in Supplementary Table 1.

Variant: Exon 2-3 Deletion (c.341-?_642+?del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: exon_loss_variant

CivicName: Exon 2-3 Deletion

MultipleGeneVariants: N/A

PatientID: 15

KindredID: 1

Case: F, 17Y0M, Spanish

DiseaseAssertion: VHL

FamilyInfo: None

CohortInfo: 36 pediatric patients with pheochromocytomas and/or parangangliomas.

CasePresentingHPOs: HP:0002666, HP:0002668 (pheochromocytoma, paraganglioma)

CaseHPOFreeText: The patient was admitted due to hypertension and secondary diabetes mellitus. She was found to have a norepinephrine secreting bilateral pheochromocytoma at age 15 and a thoracic-abdominal paraganglioma at age 17.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX

PreviouslyPublished: Yes source unknown.

SupplementalData: N/A

Variant: p.P95R (c.284C>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351750809 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.284C%3EG

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: P95R (c.284C>G)

MultipleGeneVariants: N/A

PatientID: 6

KindredID: 6

Case: 30Y0M, Sex unknown, Chinese

DiseaseAssertion: VHL

FamilyInfo: Their sister had the same deletion and presented with VHL disease type 1, and first presented with a CNS hemangioblastoma at age 21. A second sister had no mutation and was asymptomatic, and the proband's daughter had the same deletion, but was asymptomatic at the time of the study.

CasePresentingHPOs: HP:0009715; HP:0010797; HP:0005584 (Papillary cystadenoma of the epididymis, hemangioblastoma, renal cell carcinoma)

CaseHPOFreeText: CNS hemangioblastoma first presenting at age 15Y and RCC at age 22Y and EC (papillary cystadenoma of the epididymis) at 30Y

CaseNotHPOs: HP:0002666 (pheochromocytoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: Exon 2 deletion

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: exon_loss_variant

CivicName: Exon 2 deletion

MultipleGeneVariants: N/A

PatientID: 1

KindredID: 1 (A)

Case: M, 15Y0M, Hungarian

DiseaseAssertion: VHL

FamilyInfo: Both parents were healthy with no display of any mutations in the VHL gene, indicating a de novo mutation.

CasePresentingHPOs: HP:0006770; HP:0009711 (clear cell renal cell carcinoma, retinal capillary hemangioma)

CaseHPOFreeText: Patient developed bilateral retinal angioma (retinal capillary hemangioma) and had serious retinal detachment.

CaseNotHPOs: HP:0010797; HP:0002666 (hemangioblastoma, pheochromocytoma)

CaseNotHPOFreeText: MRI of the craniospinal axis could not detect any alterations. No deviation from normal values was observed in the laboratory test.

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.E55* (c.163G>T)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVar: N/A

CAID: CA351748495 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.163G%3ET

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: E55* (c.163G>T)

MultipleGeneVariants: N/A

GroupID: 22

DiseaseAssertion: assumed VHL

GroupSize: 3

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: 3 of the 573 patients discussed in this paper were found to have the following mutation belonging to 1 family. 

GroupPresentingHPOs: HP:0006880; HP:0009711; HP:0005584 (cerebellar hemangioblastoma, retinal capillary hemangioma; renal cell carcinoma)

GroupHPOFreeText: 1 patient had retinal angiomas diagnosed at the age of 15Y, 1 had cerebellar hemangioblastomas diagnosed at 20Y, and 1 member had RCC diagnosed at 38Y.

GroupNotHPOs: HP:0002666 (pheochromocytoma)

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table S1.

Variant: p.H125Qfs*7 (c.374dupA)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA2499307153 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2499307153

gnomAD: N/A

VariantEvidence: N/A

MutationType: duplication

CivicName: H125fs (c.374insA) 

MultipleGeneVariants: N/A

PatientID: 7

KindredID: 7

Case: F, 26Y0M, Ethnicity Unknown

DiseaseAssertion: assumed VHL

FamilyInfo: Positive family history of VHL.

CohortInfo: An international consortium registered patients with head and neck paragangliomas with VHL or RET gene mutations.

CasePresentingHPOs: HP:0000618; HP:0009711; HP:0010797; HP:0002668 (blindness, retinal capillary hemangioma, hemangioblastoma, paraganglioma)

CaseHPOFreeText: At 15Y she presented with loss of visual acuity, leading to the diagnosis of bilateral retinal hemangioblastomas (treated with laser and cryotherapy), with the outcome of unilateral blindness. The patient was then operated 3 times for CNS hemangioblastomas between ages 18 and 24. At age 26, she presented with a palpable lateral neck mass. CT of the head and neck revealed a 3-cm carotid body tumor (paraganglioma).

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.T105P (c.313A>C)

LegacyVariant: p.T105P

CaseProblemVariantFreeText: As the publication only provides the p., the mutation was deduced to p.T105P (c.313A>C)

ClinVarID: 496055 https://www.ncbi.nlm.nih.gov/clinvar/variation/496055/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: T105P (c.313A>C)

MultipleGeneVariants: N/A

PatientID: 11

KindredID: 11

Case: F, 36Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: There was said to be, at the time, no affected relatives

CohortInfo: An international consortium registered patients with head and neck paragangliomas with VHL or RET gene mutations.

CasePresentingHPOs: HP:0006748; HP:0002668; HP:0006476; HP:0006880; HP:0009711; HP:0000618; HP:0010797 (adrenal pheochorocytoma, paraganglioma, abnormality of the pancreatic islet cells, cerebellar hemangioblastoma, retinal capillary hemangioblastoma, blindness, hemangioblastoma)

CaseHPOFreeText: At 8Y, (in 1978), she was operated for a right pheochromocytoma; at age 13 for a contralateral pheochromocytoma; at age 15, for a 4-cm mass at the neck was diagnosed by selective arteriography as a carotid paraganglioma. The patient was then operated twice for cerebellar hemangioblastoma at age 22, leading to the diagnosis of VHL disease. At age 27, the patient was operated again for a retrocaval pheochromocytoma and for islet cell tumors. The patient was also repeatedly treated for bilateral retinal hemangioblastomas leading to blindness at age 32. At age 36, again a pheochromocytoma was removed

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.T157I (c.470C>T)

LegacyVariant: p.T157I

CaseProblemVariantFreeText: The publication only provides the p., the mutation was able to be deduced to p.T157I (c.470C>T)

ClinVarID: 223223 https://www.ncbi.nlm.nih.gov/clinvar/variation/223223/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: T157I (c.470C>T)

MultipleGeneVariants: N/A

PatientID: III

KindredID: 17

Case: Sex Unknown, 26Y0M, Danish

DiseaseAssertion: VHL

FamilyInfo: 2 other family members were found to have this VHL variant. Patient 17-I was asymptomatic. Patient 17-II presented with CNS hemangioblastoma (8Y).

CasePresentingHPOs: HP:0009711; HP:0001737 (Retinal capillary hemangioma, Pancreatic cysts)

CaseHPOFreeText: Diagnosed with VHL at age 10Y. Presented with 6 pancreatic cysts (15Y) and retinal hemangioblastoma (16Y). Age at the end of study: 26Y.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: Exon 1 Deletion (c.1-?_340+?del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: exon_loss_variant

CivicName: Exon 1 Deletion

MultipleGeneVariants: N/A

PatientID: I

KindredID: 12

Case: Sex Unknown, 21Y0M, Danish

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0009711; HP:0010797; HP:0001737 (Retinal capillary hemangioma, Hemangioblastoma, Pancreatic cysts)

CaseHPOFreeText: Diagnosed with VHL at age 5Y. Presented with 5 retinal hemangioblastoma (5Y, 13Y, 14Y) 6 CNS hemangioblastoma (15Y, 17Y) 3 pancreatic cysts (15Y). Age at the end of study: 21Y.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: Exon 1-2 Deletion (c.1-?_463+?del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: exon_loss_variant

CivicName: Exon 1-2 Deletion

MultipleGeneVariants: N/A

PatientID: 6

KindredID: 2

Case: 15Y0M, Sex and Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Recorded as a familial tumor; One other family member (Patient ID: 5) was a 29 year old patient with a bilateral pheochromocytoma. "Belonging to the same family", although the connection is unclear.

CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

CaseHPOFreeText: Unilateral pheochromocytoma reported with an age at diagnosis of 15 years of age.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET, SDHB/SDHC/SDHD

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R167W (c.499C>G)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 2219 https://www.ncbi.nlm.nih.gov/clinvar/variation/2219/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: R167W (c.499C>G)

MultipleGeneVariants: N/A

PatientID: 2

KindredID: 2

Case: M, 15Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Family history revealed hemangioblastomas and pheochromocytomas.

CohortInfo: Two patients with parasympathetic paraganglioma, previously published in 19336503 were studied.

CasePresentingHPOs: HP:0002668 (paraganglioma)

CaseHPOFreeText: At age 7, the patient had a malignant sympathetic paraganglioma in the retroperitoneum with regional lymph node metastases. Eight years later, the patient presented with a parasympathetic paraganglioma of the left carotid body.

CaseNotHPOs: N/A

CaseNotHPOFreeText: No other tumours were found.

CasePreviousTesting: SDHB/SDHC/SDHD

PreviouslyPublished: 19336503

SupplementalData: N/A

Variant: p.Y98H (c.292T>C)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 2223 https://www.ncbi.nlm.nih.gov/clinvar/variation/2223/

CAID: N/A

gnomAD: 0.00001343 https://gnomad.broadinstitute.org/variant/3-10183823-T-C

VariantEvidence: Case 2 showed LOH for markers D3S1597 and D3S1263 and was homozygous (not informative) for marker D3S1435.

MutationType: missense_variant; transition

CivicName: Y98H (c.292T>C)

MultipleGeneVariants: N/A

PatientID: 5

KindredID: 5

Case: M, 15Y0M, Spanish

DiseaseAssertion: VHL

FamilyInfo: N/A

CohortInfo: 7 VHL patients, from different regions of Spain, affected from juxtapapillary or peripheral haemangioblastomas were administered 120 mg propranolol daily.

CasePresentingHPOs: HP:0009711 (Retinal capillary hemangioma)

CaseHPOFreeText: The patient presented with a peripheral tumor in his right eye at the age of 13. He exited the trial in 2016 with no changes to the tumor size after the administration of propranolol over a one year trial.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Information obtained from Table 2.

Variant: Exon 1-3 Deletion (c.1-?_642+?del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: exon_loss_variant

CivicName: Exon 1-3 Deletion

MultipleGeneVariants: N/A

PatientID: II-1

KindredID: Family B

Case: M, 23Y0M, Ethnicity unknown

DiseaseAssertion: VHL

FamilyInfo: Family positive pedigree showing patient’s father with RCC and CNS hemangioblastoma; as well as 2 sisters with CNS/spinal and retinal hemangioblastomas

CasePresentingHPOs: HP:0010797; HP:0009711 (hemangioblastoma; retinal capillary hemangioblastoma)

CaseHPOFreeText: underwent surgery for multiple CNS hemangioblastomas at the age of 15, and at the same age multiple peripheral retinal hemangioblastomas were found in his right eye, which were treated successfully with laser photocoagulation and cryotherapy. At the age of 20, he developed a large peripheral retinal hemangioblastoma in his left eye, which was treated successfully with cryotherapy.

CaseNotHPOs: HP:0005584; HP:0002666 (renal cell carcinoma, pheochromocytoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R79P (c.236G>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351749311 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.236G%3EC

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: R79P (c.236G>C)

MultipleGeneVariants: N/A

PatientID: None (Proband)

KindredID: 1

Case: M, 18Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: The family history revealed VHL in his mother, who died at the age of 40, and in his maternal aunt and grandmother, deceased at 30 and 33 years, respectively. His mother was operated on three times for cerebellar hemangioblastomas, the first at 13 years of age. She had also been treated for bilateral retinal hemangioblastomas since the age of 19. In addition, she had surgery for a renal tumor at the age of 32 and also had pancreatic cysts. She died of the diffuse hemangioblastomas in the posterior fossa. Variant is stated to be previously identified in the family but it is not clear which members have been genetically tested.

CasePresentingHPOs: HP:0006880; HP:0002893; HP:0007663; HP:0001510; HP:0000823; HP:0009711 (Cerebellar hemangioblastoma, Pituitary adenoma, Reduced visual acuity, Growth delay, Delayed puberty, Retinal capillary hemangioma)

CaseHPOFreeText: Referred at the age of 15 for decreased visual acuity of the right eye. Growth failure with short stature for age and lack of pubertal development was noted. This was confirmed by ophthal-mologic examination which also showed bitemporal quadranopsia. Two retinal vascular lesions had already been diagnosed and photocoagulated. Cerebral MRI examination visualized a voluminous pituitary adenoma (confirmed pathologically) with suprasellar extension compressing the optic fibres invading both cavernous sinuses. It also confirmed two small cerebellar hemangioblastomas. On follow-up, MRI showed a persistent pituitary adenoma (confirmed by pathology) with numerous mitoses. A cystic part of the main hemangioblastoma was also noted in the right cerebellum image.

CaseNotHPOs: HP:0005584 (Renal cell carcinoma)

CaseNotHPOFreeText: No renal lesion was found on ultrasound examination. Renal ultrasound examination was persistently normal.

CasePreviousTesting: N/A

PreviouslyPublished: 25494863

SupplementalData: Figure 1

Variant: p.G114R (c.340G>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223193, https://www.ncbi.nlm.nih.gov/clinvar/variation/223193/

CAID: N/A

gnomAD:

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: G114R (c.340G>C)

MultipleGeneVariants: N/A

The girl just spoked to the boy with few words,and the boy is deeply fell in love to her. I am surprised at the charm the girl made to the boy.

The reason why I found this troubling is that I can't understand what kind of girl can made a boy so head over heels that he lost any patience with the daily serious of workof life.

I found this interesting because even though the boy did not fully know the girl,he has already seen her as a perfect,mind-affecting girl.

Nieuwe budgetlijn en oude indifferentiecurve.

Het substitutie effect vindt plaats op de indifferentiecurve

一篇通过 ICLR workshop 同行评审的科学论文，AI 生成成本约为 15-20 美元。相比之下，一位博士生培养成本超过 10 万美元，发表一篇顶会论文需要数月时间。这个成本差距意味着：如果这项技术成熟，科研论文的生产成本将下降数千倍。学术期刊、同行评审系统、学术出版业的整个商业模式，都将面临根本性的重构压力。

https://peterhotez.org/<br /> Peter Hotez

Your Resource For Better Health Communication & Messaging<br /> by [[Public Health Communications Collaborative]]<br /> accessed on 2026-01-15T11:50:55

New in the collection, pt. 3: Canon PW-10/15/30<br /> by [[Marcin Wichary]] in Shift Happens newsletter<br /> accessed on 2025-12-30T15:23:12

DOI: 10.1002/cne.70079

Resource: None

Curator: @scibot

SciCrunch record: RRID:ZFIN_ZDB-ALT-100506-15

What is this?

for - example - Kompromat - former house speaker Dennis Hastert - to - BBC - Dennis Hastert - sentenced to 15 months in prison - https://hyp.is/lKQYwGMHEfCpaVc_LjDjBg/www.bbc.com/news/world-us-canada-36155261

Gwneud Cyflaith / Toffee Making by [[Amgueddfa Cymru]]

Die Studie des Potsdam-Instituts für Klimafolgenforschung zeigt, dass Bioenergy with Carbon Capture and Storage (BECCS) theoretisch bis 2050 jährlich 7,5 Milliarden Tonnen CO₂ entfernen könnte. Allerdings würde dies die planetaren Belastungsgrenzen stark überschreiten, insbesondere in Bezug auf Stickstoffeintrag, Süßwasserverbrauch, Entwaldung und Biosphärenintegrität. Unter Berücksichtigung dieser Grenzen reduziert sich das Potenzial auf nur 200 Millionen Tonnen CO₂ jährlich. Die Studie betont die Notwendigkeit, neben der CO₂-Bilanz auch andere ökologische Faktoren zu berücksichtigen und schlägt vor, durch weniger Fleischkonsum Flächen für Klimaplantagen freizumachen. [Zusammenfassung generiert mit Mistral]

https://www.derstandard.at/story/3000000257365/kein-platz-fuer-klimaplantagen

2024 verzeichnete die zwölf bis ihr heißesten Monate in Europa. Über 400.000 Menschen waren direkt von den Folgen von Extremwetterereignissen betroffen. Über 30% der Flussgebiete In über 30% der Flussgebiete gab es schwere Überschwemme. Ausmaß und Erhezung, Ausmaß und Folgen der Erhezung in Europa werden systematisch in dem Berichtsteht auf Sie klimat 2024 erfasst, der von Copernicus und der WMU veröffentlicht wurde. https://www.theguardian.com/environment/2025/apr/15/europe-storms-floods-and-wildfires-in-2024-affected-more-than-400000

"Scholar of racial difference in the early modern Atlantic world have detected a decline in the contradictions after about the mid-seventeenth century and a rise of more uniformly negative appraisals of Africa and Africans." p. 15

What lead to this shift? Did it have some connection to the need of dehumanization to condone the act of slavery in the context of the Atlantic Slave trade?

Dem amerikanischen Historiker Künstlubodien zufolge ist ein Vorbild für die Trump-Administration weniger der historische Faschismus in Italien und Deutschland als die kapitalistische oligarchien Herrschaft in Saudi Arabien. Tramp Wolle die USA zu einem modernen Petro stattmachen. Er wolle dazu die Weltweite Abhängigkeit von den USA nicht nur beim Öl ausnutzen. Außerdem stütze er sich auf die enorm finanziellen Ressourcen Saudi-Abiens. Der S.A. in den New York Times stützt diese Tese mit einer Vielzahl von Einzelbeobachtungen. https://www.nytimes.com/2025/03/15/opinion/trump-saudi-arabia-america.html

Though parents grudge, and you, w'are met, <br /> And cloistered in these living walls of jet.

The speaker tells the listener to forget societal norms and barriers, telling them that they have already met in a sacred place, a reference to the temple or flea. The flea creates a close, private area for the two of them to be free from the view of others.

> for - stats - addiction - alcohol - average duration - 15 years

https://en.wikipedia.org/wiki/Knocking_on_wood

https://www.derstandard.at/story/3000000257317/sicherheitsexperten-warnen-klimapolitik-stellt-die-eu-vor-eine-zerreissprobe

https://www.derstandard.at/story/3000000252982/der-golfstrom-ist-stabiler-als-geglaubt

Ein Hauptgrund für die Feuer in Los Angeles ist, dass die globale Erhitzung den Beginn der Regenfälle nach hinten verschoben hat. Dieses Phänomen war von Wissenschftlern vorausgesagt worden. Bisher gab es in Kalifornien um diese Zeit keine Waldbrände. Gespräch mit dem Forscher Eric Rigolo die Gründe der Katastrophe https://www.liberation.fr/environnement/incendies-a-los-angeles-nous-assistons-a-un-basculement-important-dans-la-saisonnalite-des-feux-20250115_2RPAYNV4HRDW7MAMEZQJBZT2YM/

这篇论文介绍了一个名为ROSCOE的度量标准套件，用于评估逐步骤推理的性能。ROSCOE是一套可解释的、无监督的自动评分系统，旨在改进和扩展之前的文本生成评估指标。该研究通过设计一个推理错误的分类学，并在常用的推理数据集上收集合成和人类评估分数，来评估ROSCOE相对于基线指标的表现

for - stats - job satisfaction - Gallup poll 2024 - engaged employees worldwide - 15% - Gallup CEO - Jim Clifton - from - Youtube Ma Earth channel interview - Devcon 2024 - Cosmo Local Commoning with Web 3 - Michel Bauwens - 2025, Jan 2 - https://hyp.is/FiFXpNBMEe-n_Jc4-PJ5_A/www.youtube.com/watch?v=UCkLHj6r7y8

for - paraphrase - history of labor - SOURCE - Youtube Ma Earth channel interview - Devcon 2024 - Cosmo Local Commoning with Web 3 - Michel Bauwens - 2025, Jan 2 - to - stats - Gallup Chairman's Blog - world poll 2024 - 15% of employees worldwide are engaged - SOURCE - Youtube Ma Earth channel interview - Devcon 2024 - Cosmo Local Commoning with Web 3 - Michel Bauwens - 2025, Jan 2

paraphrase - history of labor - Michel gives a nice succinct summary of the broad strokes of the history of labor over the last few millennia: - Civilizations have begun as slave-based societies first - Then when the Christian revolution occurred after the fall of the Roman Empire, "Ora et Labora (Pray and Work)" was adopted to transform work into a spiritually meaningful endeavor - Then in the 16th century, this philosophy was replaced by turning labor into a commodity, where it has remained ever since, - resulting in a world where 85% of those surveyed say they are not engaged with their job

to - stats - Gallup Chairman's Blog - world poll 2024 - 15% of employees worldwide are engaged - https://hyp.is/iOlXbNBOEe-t6hdOWtvTYw/news.gallup.com/opinion/chairman/212045/world-broken-workplace.aspx

for - question - what if the children were identified to come back? - source - article - Substack - One of the biggest wealth transfers in U.S. history just commenced. Are you aware of it? - Alexandra Fasulo - 2024, Oct 15

for - article - Substack - One of the biggest wealth transfers in U.S. history just commenced. Are you aware of it? - Alexandra Fasulo - 2024, Oct 15

• opportunity - regenerative agriculture and rewilding - US farmers retiring in the next 20 years - largest transfer in US history - land trusts ?

• referred by - Kim Chapple

for - progress trap - AI superintelligence - interview - AI safety researcher and director of the Cyber Security Laboratory at the University of Louisville - Roman Yampolskiy - progress trap - over 99% chance AI superintelligence arriving as early as 2027 will destroy humanity - article UofL - Q&A: UofL AI safety expert says artificial superintelligence could harm humanity - 2024, July 15

for - stats - most people in America agree on 85 - 90% of issues - unpack why and how the 10 - 15% is made so divisive

Who was the leader/emperor of Russia at this time?

Cite your sources!

Finnland hatte sich beim Ziel der CO2-Neutralität 2035 darauf verlassen, dass große Mengen von CO2 von Wäldern, Böden und Feuchtgebieten absorbiert werden. Inzwischen ist das Land dort keine Kohlenstoffsenke mehr. Dazu trägt die globale Erhitzung selbst bei, durch die viele Bäume sterben, aber auch die Abholzung des Waldes. Finnland ist ein Beispiel für die Schwächung der ländlichen Kohlenstoffsenken, von der viele Länder betroffen sind. https://www.theguardian.com/environment/2024/oct/15/finland-emissions-target-forests-peatlands-sinks-absorbing-carbon-aoe

for - stats - earth system boundary - biodiversity - intact natural systems - 15% below ESB in 2018

WirtschaftsWoche: Hintergrundbericht zur geplanten Fusion der Petrochemie-Sparten von OMV und Adnoc. Die Adnoc will mit #Bourouge einen Petrochemie-Großkonzern aufbauen, der dann statt Treibstoffe scheinbar saubere Produkte wie Kunstdünger und Plastik verkauft und auf Recycling und Kreislaufwirtschaft ausgerichtet ist. Dazu ist man auch an einer Übernahme von Covestro und Wintershall interessiert. Der Konzern soll zur Hälfte der OMV gehören. https://www.wiwo.de/unternehmen/industrie/chemieindustrie-was-hinter-dem-megageschaeft-zwischen-omv-und-adnoc-steckt/29560900.html

https://www.derstandard.at/story/3000000199758/pr228sidenten-von-venezuela-und-guyana-beraten-252ber-streit-um-essequibo

Neue Daten der "Global Oil and Gas Exit List" zeigen, dass die Adnoc, die Öl- und Gasgesellschaft der Vereinigten Arabischen Emirate, die weitreichendsten Expansionspläne aller Ölfirmen hat. Die rolle des Adnoc-Chefs Sultan Al Jaber als Präsident der #COP28 sei "lächerlich". Seit 2021 sind weltweit 140 Milliarden Dollar in die Exploration neuer Öl- und Gasfelder geflossen. 96% der 700 im Explorationsgeschäft tätigen Firmen explorieren weiter, 1000 Firmen arbeiten an neuen Pipelines, LNG Terminals und anderer Infrastruktur zur Distribution von Öl und Gas. https://www.theguardian.com/environment/2023/nov/15/cop28-host-uae-oil-plans-data

https://www.nytimes.com/2024/04/15/climate/al-gore-climate-activism.html

https://www.nytimes.com/2024/04/15/climate/coral-reefs-bleaching.html

https://www.theguardian.com/environment/2024/apr/15/great-barrier-reef-coral-bleaching-global-heating

https://www.theguardian.com/environment/2024/apr/15/climate-crisis-deadly-ocean-upswells-cold-water-study

Die Dürren der letzten 20 Jahre waren schlimmer als in den 2100 Jahren davor. Bericht über eine klimahistorische Studie, die von den Isotopen in den Jahresringen von Eichen ausgeht.

Studie: https://www.nature.com/articles/s41561-021-00698-0

Aufgrund der Dürren und anderer Extrem-Ereignisse wird die Trinkwasser-Versorgung in vielen Communities im Einzugsgebiet des Mississippi prekär. Der Süden Louisianas wird von eindringendem Salzwasser bedroht, Dabei sind die Folgen der schweren Hurricanes der vergangenen Jahre noch nicht überwunden. Immer mehr Menschen wollen die Gegend verlassen. https://www.nytimes.com/2023/11/15/us/louisiana-saltwater-climate.html

Showing the parallel between him and other babies of his age, he describes that he did not shout "Miez, Miez, Miez, Miez", which translates to "no, no, no, no" in old germanic dialects like the other children. But instead, in a polar opposite manor, yelled "high, sturdy and big voice" shouted drink, drink, drink. Showing from an early age leadership, confidence, and "greatness".

Borealis-Chef Thomas Gangl wechselt zu einem anderen Konzern. Der Artikel enthält Grundinformationen zu den wechselseitigen Beteiliigungen von OMV und Adnoc.Die vollständige Fusion der Petrochemie von OMV und Adnoc ist noch nicht beschlossen. https://www.derstandard.at/story/3000000211778/omv-tochter-borealis-verliert-inmitten-heikler-verhandlungen-ihren-chef

https://www.axios.com/2024/02/15/amazon-rainforest-closer-to-tipping-points

Interview mit dem Blackrock-Portfoliomanager Evy Hambro zu den Folgen der Energiewende für die Rohstoff-Märkte und einzige ihrer geopolitischen Implikationen. Grundaussagen: Durch erneuerbare Energien wird die Wirtschaft rohstoffintensiver und die Rohstoffpreise steigen. Auch der Bergbau ist bisher CO2-intensiv. Das Festhalten an Wachstum führt zu Investitionen in Kerneenergie und Uran-Bergbau. China beherrscht vor allem die Mitte der Lieferkette für wichtige Rohstoffe. https://www.handelsblatt.com/finanzen/maerkte/devisen-rohstoffe/blackrock-experte-energiewende-koennte-mineralienpreise-in-die-hoehe-treiben/100013162.html