, VHL, RET, and MAX germline and somatic mutations have been reported in 3–25%, 13–9%, 5–5%, and 1–3% of tumours, respectively [33]. Recently activating mutations in HIF2A and HRAS were reported in a subset of these tumours [6, 7, 19, 20]. Whilst HIF2A mutations may be found in multiple tumours from patients without a detectable germline mutation (suggesting low level constitutional mosaicism) or occasionally as a germline mutation [5], to date HRAS mutations have only been detected as somatic changes (germline HRAS mutations are associated with Costello syndrome but PCC/PGL/HNPGL are apparently not a feature of this disorder) [34].
6 Matching Annotations
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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VHL: c.374A>C, p.His125Pro
A cohort of 64 pheochromocytoma and paragangliomas were screened for a BRAF mutation using direct Sanger sequencing and QRT-PCR. Genomic DNA was extracted from fresh or frozen peripheral blood. Germline mutations of VHL, SDHB, SDHD, and RET genes were also observed. The VHL mutation c.374A>C (p.His125Pro) was reported in patient #42, a 24Y male with bilateral pheochromocytoma. No family history was reported here.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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PMID: 21461997
4 paediatric patients presenting with pheochromocytomas and paragangliomas were reported. Upon genetic testing of peripheral blood leukocytes on the VHL, SDHB, SDHC, SDHC, and RET genes, 1 patient was found to have the c.374A>C germline mutation. At 13Y the patient had bilateral adrenal pheochromocytoma and retinal capillary hemangiomas. Now, 19Y, he remains in complete remission. Family screening showed the absence of the mutation in the asymptomatic mother; the father was not analyzed. Other family history was negative for VHL syndrome and PCCs.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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PatientID: Carrier 7 (niece to proband 3)
KindredID: 1
Case: M, Age Unknown, Chinese
DiseaseAssertion: Asymptomatic
FamilyInfo: The family with PCCs includes 56 members of 4 generations, and is from Gansu Province. Among them, 7 extended over 3 generations were diagnosed as PCCs. One died before admission and another died due to a cardiovascular incident. Five were initially evaluated; evaluation included medical history, physical examination, abdominal ultrasonography, CT or MRI and laboratory tests. All 5 probands of this family underwent surgical resection. The tumors were benign under pathological examinations. There were no recurrence and malignant transformation over the period of up to 23-year follow-up. Twenty members, including 5 live patients and 15 direct relatives, accepted genetic examination.
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: N/A
PreviouslyPublished: N/A
SupplementalData: N/A
Variant: p.H125P (c.374A>C)
LegacyVariant: N/A
CaseProblemVariantFreeText: N/A
ClinVarID: 223201, https://www.ncbi.nlm.nih.gov/clinvar/variation/223201/
CAID: N/A
gnomAD: N/A
VariantEvidence: N/A
MutationType: missense_variant;transversion
CivicName: H125P (c.374A>C)
MultipleGeneVariants: N/A
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PatientID: Carrier 1 (sister to proband 1)
KindredID: 1
Case: F, 29Y0M, Chinese
DiseaseAssertion: VHL
FamilyInfo: The family with PCCs includes 56 members of 4 generations, and is from Gansu Province. Among them, 7 extended over 3 generations were diagnosed as PCCs. One died before admission and another died due to a cardiovascular incident. Five were initially evaluated; evaluation included medical history, physical examination, abdominal ultrasonography, CT or MRI and laboratory tests. All 5 probands of this family underwent surgical resection. The tumors were benign under pathological examinations. There were no recurrence and malignant transformation over the period of up to 23-year follow-up. Twenty members, including 5 live patients and 15 direct relatives, accepted genetic examination.
CasePresentingHPOs: HP:0002666 (Pheochromocytoma)
CaseHPOFreeText: Bilateral PCC diagnosed at 17Y and did not have any other clinical presentations. Stated as having VHL type IIC.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: N/A
PreviouslyPublished: N/A
SupplementalData: N/A
Variant: p.H125P (c.374A>C)
LegacyVariant: N/A
CaseProblemVariantFreeText: N/A
ClinVarID: 223201, https://www.ncbi.nlm.nih.gov/clinvar/variation/223201/
CAID: N/A
gnomAD: N/A
VariantEvidence: N/A
MutationType: missense_variant;transversion
CivicName: H125P (c.374A>C)
MultipleGeneVariants: N/A
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PatientID: Carrier 6 (nephew to proband 3)
KindredID: 1
Case: M, Age Unknown, Chinese
DiseaseAssertion: Asymptomatic
FamilyInfo: The family with PCCs includes 56 members of 4 generations, and is from Gansu Province. Among them, 7 extended over 3 generations were diagnosed as PCCs. One died before admission and another died due to a cardiovascular incident. Five were initially evaluated; evaluation included medical history, physical examination, abdominal ultrasonography, CT or MRI and laboratory tests. All 5 probands of this family underwent surgical resection. The tumors were benign under pathological examinations. There were no recurrence and malignant transformation over the period of up to 23-year follow-up. Twenty members, including 5 live patients and 15 direct relatives, accepted genetic examination.
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: N/A
PreviouslyPublished: N/A
SupplementalData: N/A
Variant: p.H125P (c.374A>C)
LegacyVariant: N/A
CaseProblemVariantFreeText: N/A
ClinVarID: 223201, https://www.ncbi.nlm.nih.gov/clinvar/variation/223201/
CAID: N/A
gnomAD: N/A
VariantEvidence: N/A
MutationType: missense_variant;transversion
CivicName: H125P (c.374A>C)
MultipleGeneVariants: N/A
Tags
- cDNAposition:374
- inferred_gene_source:RefSeq
- AgeOfPresentation:pheochromocytoma:29
- AminoAcidChange:HIStoPRO
- ClinVarID:223201
- Ethnicity:Chinese
- inferred_gene_hgnc:12687
- MutationType:missense_variant;transversion
- DiseaseEntity:VHL
- DiseaseEntity:Asymptomatic
- DiseaseEntity:pheochromocytoma
- AssumedRefSeq:NM_000551.3
- Mutation:Germline
- CivicName:H125P(c.374A>C)
- ClinVarID:Yes
- Familial
- ProteinPosition:125
- InheritancePattern:AutosomalDominant
- VHL Hypothesis Annotation
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