Hypothesis

The patient's father, now 51 years old, was found to have an angioma of the glans penis and had had surgery for a mandibular cyst and epididymal cystadenomas at age 43 years. Hence, we suspected that the father had an attenuated form of VHL. Indeed, abdominal ultrasonography and total-body magnetic resonance imaging (MRI) revealed a 2.3-cm cyst in his right kidney. His blood pressure and levels of plasma free metanephrines, fractionated urinary metanephrines, chromogranin A were normal. The other three first-degree relatives were normal both clinically and biochemically.

PatientID: DHPLC 1

KindredID: 1

Case: M, 51Y0M, Unknown Ethnicity

DiseaseAssertion: Assumed VHL

FamilyInfo: The patient’s daughter (DHPLC 1) had a pheochromocytoma at 11Y. At 18Y, she had a pheochromocytoma in the contralateral adrenal gland and two concurrent paragangliomas of the abdominal aorta and urinary bladder. At 25Y, she was found to have a right frontal meningioma. A family history obtained from his daughter’s other parent, one son and one other daughter (not DHPLC 1) was uninformative. The patient’s relatives (except for his daughter) were normal both clinically and biochemically.

CasePresentingHPOs: HP:0001028; HP:0000277; HP:0009715; HP:0000107 (Angioma, abnormality of the mandible, papillary cystadenoma of the epididymis, renal cyst)

CaseHPOFreeText: The patient had an attenuated VHL phenotype caused by mosaicism which led to what initially appeared to be a de novo mutation in his daughter (DHPLC 3). The patient was found to have an angioma of the glans penis and had had surgery for a mandibular cyst and epididymal cystadenomas at age 43Y. Abdominal ultrasonography and total-body magnetic resonance imaging (MRI) conducted at the time of the study (51Y) revealed a 2.3-cm cyst in his right kidney. His blood pressure and levels of plasma free metanephrines, fractionated urinary metanephrines, chromogranin A were normal.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

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

LegacyVariant: p.R161Q (c.695G>A)

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

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: R161Q(c.482G>A)

MultipleGeneVariants: N/A

InheritancePattern:AutosomalDominant DiseaseEntity:renalcyst DiseaseEntity:papillarycystadenomaoftheepididymis DiseaseEntity:hemangioma AgeOfPresentation:renalcyst:51 AgeOfPresentation:hemangioma:43 AgeOfPresentation:papilarycystadenomaoftheepididymis:43 Mutation:Germline Mutation:Somatic RefSeq:N/A AssumedRefSeq:AF010238.1 cDNAposition:482 ProteinPosition:161 AminoAcidChange:ARGtoGLN ClinVarID:Yes ClinVarID:182983 MutationType:missense_variant;transition CivicName:R161Q(c.482G>A) FamilyPedigree Familial inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation

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