A cohort of 36 PCCs and four functional PGL tumours were analysed by exome-seq and high-density SNP-array analysis using tumor paired blood. This specified germline VHL mutation (tumor ID: V-PH-29T) belonged to a female diagnosed with bilateral phaeochromocytoma at age 8Y, surgery at 10Y. She also had a personal history including extra adrenal abdominal phaeochromocytoma and lymph node involvement at age 8yrs. The p.V84L (c.250G>C) VHL mutation was also accompanied by an additional germline variant: MEN1: c.512G>C (p.Arg171Pro). It was stated that there were no familial cancers/syndromic illnesses with this patient. Additionally, this patient was likely previously published in PMID: 26796762 (ID: WM02).

PatientID: V-PH-29T

KindredID: 5

Case: F, 10Y0M, Ethnicity Unknown

DiseaseAssertion: assumed VHL

FamilyInfo: No familial cancers/syndromic illnesses

CasePresentingHPOs: HP:0002666; HP:0006737; HP:0002733 (pheochromocytoma, extraadrenal pheochromocytoma, abnormality of the lymph nodes)

CaseHPOFreeText: diagnosed with bilateral phaeochromocytoma at age 8Y, surgery at 10Y. She also had a personal history including extra adrenal abdominal phaeochromocytoma and lymph node involvement at age 8yrs

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET, SDHA, SDHB, SDHC, TMEM127

PreviouslyPublished: Possibly; 26796762 (ID: WM02)

SupplementalData: Yes (see table S1 and S10)

Variant: p.V84L (c.250G>C)

LegacyVariant: Given as ENSP00000256474.2:p.Val84Leu (G>C)

CaseProblemVariantFreeText: N/A

ClinVarID: 229860 https://www.ncbi.nlm.nih.gov/clinvar/variation/229860/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: V84L (c.250G>C)

MultipleGeneVariants: Germline, MEN1, c.512G>C (p.Arg171Pro)

This report studied the prevalence of germline variants in Japanese PPGL patients. Of the 370 PPGL original Japanese probands, this cohort consisted of 15 patients with pheochromocytoma and/or paragangliomas with germline VHL varaints. Blood samples were used to examine 7 genes: MAX, SDHB, SDHC, SDHD, TMEM127, VHL, and RET, using Sanger sequencing. Of these 15 VHL patients: 10 had bilateral PCC, 4 had PCC with abdominal/thoracic PGL, and one had metastatic PPGL. The variant V84L (c.250G>C) was one of the 15 found in a patient with PPGL. Their family history or further manifestations were not detailed.