GroupID: 14

DiseaseAssertion: VHL

Group size: 2

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, two individual was suspected of VHL disease, but neither developed RH.

GroupPresentingHPOs: N/A

GroupHPOFreeText: N/A

GroupNotHPOs: HP:0009711 (retinal capillary hemangioma)

GroupNotHPOFreeText: This VHL patients did not present with retinal capillary hemangioma.

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Table S1

Variant: p.R64P (c.191G>C)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 2226, https://www.ncbi.nlm.nih.gov/clinvar/variation/2226/

CAID: N/A

gnomAD: N/A

VariantEvidence: Chr3(GRCh37): g.10183722G>C

MutationType: missense_variant; transversion

CivicName: R64P (c.191G>C)

MultipleGeneVariants: N/A

PatientID: 4

KindredID: 4

Case: F, 23Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: The patient had a family specific p.Arg64Pro mutation, and VHL disease had a heterogeneous presentation in the family. The patient’s father initially presented with bilateral pheochromocytomas and clear cell renal carcinoma, and the patient’s son underwent unilateral adrenalectomy for pheochromocytoma at the age of 7.

CasePresentingHPOs: HP:0002668 (Paraganglioma)

CaseHPOFreeText: The patient was asymptomatic and presented with a palpable mass on the left side of the neck during a routine check-up. Somatostatin receptor scintigraphy revealed a hotspot near the left carotid artery, which indicated a paraganglioma. The paraganglioma was 2.5cm in size, and histological examination of it post-resection confirmed it was a paraganglioma. The patient did not present with any later tumors, although the length of follow-up is not specified.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R64P (c.191G>C)

ClinVarID: 2226, https://www.ncbi.nlm.nih.gov/clinvar/variation/2226/

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: R64P(c.191G>C)

MultipleGeneVariants: N/A

PatientID: 1

KindredID: 1

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: No family information provided.

CasePresentingHPOs: HP:0002666; HP:0002668 (Pheochromocytoma; paraganglioma)

CaseHPOFreeText: Patient had pheochromocytoma and/or paraganglioma (table 2).

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R64P (c.191G>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 2226, /www.ncbi.nlm.nih.gov/clinvar/variation/2226/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant, transversion

CivicName: R64P (c.191G>C)

MultipleGeneVariants: N/A

PatientID: 5

KindredID: 5

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL - asymptomatic

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: No tumors were reported in this patient: it was stated that they present an additional rare disease: the patient is heterozygous for CLN5protein in the neuronal ceroid lipofuscinosis rare disease. It is thus hypothesized that the CLN5 mutation in this VHL patient offers a protective effect to prevent tumors.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CLN5

PreviouslyPublished: N/A

SupplementalData: Yes

Variant: p.R64P(c.191G>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 2226 https://www.ncbi.nlm.nih.gov/clinvar/variation/2226/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: R64P (c.191G>C)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 1

Case: F, 64Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0010797; HP:0000504; HP:0006770; HP:0002666; HP:0001737; HP:0009711; HP:0002403; HP:0020036; HP:0000969; HP:0025163 (Hemangioblastoma, Abnormality of vision, Clear cell renal cell carcinoma, Pheochromocytoma, Pancreatic cysts, Retinal capillary hemangioma, Positive Romberg sign, Upper limb dysmetria, Edema, Abnormality of optic chiasm morphology)

CaseHPOFreeText: Presented at age 64 with a known large suprasellar hemangioblastoma, and history of right eye enucleation presented with worsening vision of her remaining left eye. The patient had a past history of severe VHL disease with bilateral clear cell renal cell carcinomas, bilateral pheochromocytomas, pancreatic cysts, retinal HBs, and multiple CNS HBs. Neurological exam was significant for Romberg sign and mild dysmetria of bilateral upper extremities. A visual field test of the left eye revealed new onset inferior temporal quadrantanopsia. Magnetic resonance imaging confirmed a slowly growing suprasellar hemangioblastoma within the circle of Willis with increased optic tract edema and compression of the optic chiasm.

CaseNotHPOs: HP:0007686; HP:0000496 (Abnormal pupillary function, Abnormality of eye movement)

CaseNotHPOFreeText: Left eye extraocular movements and pupillary reaction intact.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

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

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

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

CAID: N/A

gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T

VariantEvidence: VHL-HBs demonstrated strong expression patterns for all receptor subtypes except SSTR3 (more info available in “Results”).

MutationType: missense_variant;transition

CivicName: R167W (c.499C>T)

MultipleGeneVariants: N/A

PatientID: 552

KindredID: 1

Case: F, 7Y4M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: The patient’s mother had pheochromocytoma, and the patient’s maternal second-degree relatives had renal cell carcinoma and systemic lupus erythematosus/rheumatoid arthritis.

CasePresentingHPOs: HP:0002666; HP:0001085 (Pheochromocytoma, papilledema)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R64P (c.191G>C)

ClinVarID: 2226, https://www.ncbi.nlm.nih.gov/clinvar/variation/2226/

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: R64P(c.191G>C)

MultipleGeneVariants: N/A

PatientID: III-4

KindredID: 1

Case: 34Y0M, Sex and Ethnicity Unknown

DiseaseAssertion: pheochromocytoma

FamilyInfo: Family suggesting incomplete penetrance of a VHL gene germline mutation. Mutation (p.R64P) was found in a family with 6 patients total with three generations. The earliest patient described (I-1) presented with renal cell carcinoma (age at diagnosis 48 years), 1 of their 6 children (II-1) at age 59 had no typical VHL manifestations after annual clinical monitoring and suggest non-penetrance in the patient; the second of 6 children (II-3), then aged 51, had bilateral pheochromocytoma diagnosed age 14. Their only child (III-5) had a paraganglioma with an age of diagnosis of 29 years, and a renal cyst. Patient II-1 had 4 children - one (III-1; aged 40) who presented as a carrier with no typical VHL manifestations after annual clinical monitoring; and another 32 years old presenting with pheochromocytoma. (See Figure 2 for pedigree)

CasePresentingHPOs: HP:0002666 (pheochromocytoma)

CaseHPOFreeText: Bilateral pheochromocytoma diagnosed at age 34

CaseNotHPOs: N/A

CaseNotHPOFreeText: Unclear as to whether testing for other manifestations was conducted

CasePreviousTesting: N/A

PreviouslyPublished: Previously reported, HGMD (Human Gene Mutation Database: http://uwcmml1s.uwcm.ac.uk/uwcm/mg/search/120488.html)

SupplementalData: N/A

Variant: p.R64P (c.191G>C)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 2226 https://www.ncbi.nlm.nih.gov/clinvar/variation/2226/

CAID: CA020089 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.191G%3EC

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: R64P (c.191G>C)

MultipleGeneVariants: N/A

PatientID: N/A (case)

KindredID: 1

Case: F, 18Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Not relevant - She was the first child of consanguineous parents. Her family history was notable for type 2 diabetes and dyslipidemia but no history of pheochromocytoma, paraganglioma, unexplained sudden death, or condition relevant to VHL. However, the family screening for VHL has not been performed.

CasePresentingHPOs: HP:0006748; HP:0000819; HP:0008200 (adrenal pheochromocytoma; Diabetes mellitus; hyperparathyroidism)

CaseHPOFreeText: First brought to clinic for newly diagnosed diabetes mellitus and severe arterial hypertension. As symptoms, the patient complained of headaches, palpitations, diaphoresis, and hot flashes since one month. She reported also asthenia and body weight loss of five kilograms in two weeks. Pheochromocytoma was confirmed. CT showed adrenal masses: Right measuring 35×55×70mm, and left measuring 24×27mm. She underwent a bilateral adrenalectomy in two steps. Pathological examination confirmed bilateral adrenal pheochromocytomas. 12 months post, follow up is clear.

CaseNotHPOs: N/A

CaseNotHPOFreeText: Thyroid, abdominal, and neurological examinations were normal.

CasePreviousTesting: RET

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R64P (c.191G>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 2226 https://www.ncbi.nlm.nih.gov/clinvar/variation/2226/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: R64P (c.191G>C)

MultipleGeneVariants: N/A

PatientID: 20

KindredID: 900

Case: Sex unknown, Age unknown, French

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0030405 (pancreatic endocrine tumour)

CaseHPOFreeText: N/A

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P95Rfs*64 (c.284delC)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA2497030172 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2497030172

gnomAD: N/A

VariantEvidence:N/A

MutationType: minus_1_frameshift_variant

CivicName: P95Rfs*64 (c.284del)

MultipleGeneVariants: N/A

PatientID: 100

KindredID: 100

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: Paraganglioma

FamilyInfo: N/A

CasePresentingHPOs: HP:0002668 (paraganglioma)

CaseHPOFreeText: The patient had multiple paragangliomas.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Patient information pulled from Supplemental Table 1. There is additional tumour specific information in Supplemental Table 2.

Variant: p.R64P (c.191G>C)

ClinVarID: 2226 https://www.ncbi.nlm.nih.gov/clinvar/variation/2226/

gnomAD: N/A

VariantEvidence: Membrane CA9 immunostaining was observed (supplemental table 1).

MutationType: missense_variant;transversion

CivicName: R64P(c.191G>C)

MultipleGeneVariants: N/A

PatientID: F119

KindredID: 1

Case: F, 20Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0002666 (pheochromocytoma)

CaseHPOFreeText: The patient had a pheochromocytoma in the left adrenal gland. It was measured to be 3 cm in size and 23 grams in weight.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET/SDHB/SDHD

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R64P(c.191G>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 2226 https://www.ncbi.nlm.nih.gov/clinvar/variation/2226/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: R64P(c.191G>C)

MultipleGeneVariants: N/A

When did the United States finally recognize the Soviet Union?

Cite your source(s)!

for - stats - U.S. working class - 666.1% of civilian workforce between 18 and 64

Résumé de la vidéo [00:00:00][^1^][1] - [00:22:25][^2^][2]:

Cette vidéo présente le témoignage de Sylvain Huard, un jeune homme de 24 ans, et de sa mère Laurence, qui partagent leur expérience de vie avec le handicap de Sylvain. Ils discutent des défis rencontrés, de l'impact sur la famille, et de l'importance du soutien familial.

Points forts: + [00:00:00][^3^][3] L'importance du soutien familial * Les parents s'adaptent et acceptent leur enfant, handicapé ou non * La famille peut être encore plus liée par les défis du handicap + [00:01:38][^4^][4] L'expérience de la parentalité et la fratrie * Discussion sur la parentalité d'un enfant handicapé et les répercussions sur les frères et sœurs * Sylvain et sa mère retracent son parcours depuis l'enfance jusqu'à l'âge adulte + [00:03:00][^5^][5] Le parcours diagnostique et scolaire * Sylvain a été confronté à des difficultés scolaires et à un long parcours diagnostique * Il a été diagnostiqué avec un TED non spécifié à l'âge de 14 ans après de nombreux défis + [00:20:59][^6^][6] Le témoignage du frère de Sylvain * Floriant partage son expérience en tant que frère d'une personne handicapée * Il parle de l'impact du handicap de Sylvain sur sa propre vie et leur relation actuelle

Résumé de la vidéo [00:22:27][^1^][1] - [00:42:19][^2^][2]:

Cette vidéo présente un témoignage personnel sur le parcours hors-norme de Sylvain, un jeune homme ayant des troubles du développement. Il partage ses expériences d'intimidation à l'école, les défis de l'intégration sociale et son évolution vers une vie indépendante et épanouie.

Points forts: + [00:22:27][^3^][3] Les défis de l'école * Sylvain a subi de la violence et de l'incompréhension * Il a été victime d'intimidation par les élèves et maltraité par les adultes * Ces expériences ont eu un impact profond sur lui et sa famille + [00:25:07][^4^][4] La résilience et la croissance * Malgré les difficultés, Sylvain a développé une maturité et une bienveillance remarquables * Il a appris à se protéger et à s'adapter à son environnement * Sa famille reconnaît sa transformation en une personne empathique et capable + [00:31:00][^5^][5] L'adoption d'un nouveau mode de vie * Sylvain a choisi une vie d'itinérance, trouvant du bonheur dans la simplicité * Il a surmonté les obstacles avec créativité et autonomie * Cette nouvelle vie lui a apporté une liberté et une satisfaction personnelle + [00:39:01][^6^][6] Le voyage comme thérapie * Les voyages ont permis à Sylvain de se découvrir et de s'épanouir * Il a parcouru des milliers de kilomètres, gagnant en confiance et en indépendance * Sa mère exprime sa fierté et son soulagement de le voir heureux et accompli

https://www.reddit.com/r/c64/comments/1bg0ja1/does_anyone_have_the_zettelkasten_program_from/

The speaker is directing the song towards the theme ‘freedom’ “give me freedom,fire,reason”these metaphors used by the writer is saying that these are what is needed to take things to a higher level as seen in the following phrase,”take me higher”Freedom represents the power of right to act or speak,which shows the intensity the writer wants to take things higher.The word fire also could represent inspiration,which also is a powerful thing to use to take things more bigger.

AssayResult: 4.6

AssayResultAssertion: Normal

StandardErrorMean: 0.57

HGVS: NM_024675.3:c.3320T>C p.(Leu1107Pro)

AssayResult: 13.87

AssayResultAssertion: Abnormal

ReplicateCount: 2

StandardErrorMean: 1.32

Comment: Exact values reported in “Source Data” file.

AssayResult: 10.53

AssayResultAssertion: Abnormal

ReplicateCount: 2

StandardDeviation: 2.79

StandardErrorMean: 1.97

Comment: Exact values reported in “Source Data” file.

HGVS: NM_024675.3:c.514_517delTCTG p.(S172fs)

AssayResult: 14.8

AssayResultAssertion: Abnormal

ReplicateCount: 27

StandardErrorMean: 2.5

Comment: This variant had partial loss of function of peak current (10-50% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)

HGVS: NM_198056.2:c.4925G>A p.(Gly1642Glu)

DISOLUCIÓN ANTICIPADA DE LAS CÁMARAS Cuya finalidad es reforzar la mayoría parlamentaria del gobierno a base de una nueva elección electoral. La iniciativa es que el Presidente tenga deliberación con el Consejo de Ministros. Sus aspectos son : 1 Que el decreto este firmado por el Rey y refrendado por el Presidente. art 64 2 Debe de haber una convocatoria electoral. art 68 3 Puede afectar a una o las dos Cámaras. Título III. Sus límites son: -No puede haber una disolución anticipada mediante una moción de censura. art 113. -No puede haber una nueva disolución sin haber pasado un año del anterior. art 115 y art 99 -No puede haber disolución en los supuestos del art.116.

Part V and §§.64, 65, 69, 71, 80, and 82 of the Constitution Act, 1867.