GroupID: 46

DiseaseAssertion: VHL

GroupSize: 2

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: Japanese

GroupAgeRange: N/A

GroupInfo: 2 individuals from a single family (ID 46).

GroupPresentingHPOs: HP:0001732; HP:0005584 (Abnormality of the pancreas, Renal cell carcinoma)

GroupHPOFreeText: Renal cell carcinoma (2/2) and pancreatic tumor or cyst (unspecified) (1/2).

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

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: 8634692

SupplementalData: N/A

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

LegacyVariant: c.566T>C

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: N/A

A previous study of 26 Japanese, VHL families was extended to 41 additional families. Germline mutations were detected in 55 of 77 Japanese families using SSCP, direct sequencing, and Southern Blot analysis of peripheral blood samples. The L118P (c.353T>C) germline missense mutation was found in a VHL type 1 family presenting with renal cell carcinoma (2/2) and pancreatic tumor or cyst (unspecified) (1/2) (family ID 83). This family was previously reported in PMID 8634692.

Screening of 92 unrelated patients with VHL disease revealed 61 DNA variants. No variants were found in 96 control cases. Direct sequencing on peripheral blood was systematically performed on exon 1 PCR products. Southern blotting was used to search for larger alterations to the gene. The L118P (c.353T>C) missense mutation was found in 3 VHL type 1 (no pheochromocytoma) family members (patient/proband no. V27). Ten unaffected family members were screened with no evidence of the L188P variant. This family was stated as being previously published in PMID 15300849.