European Journal of Human Genetics - Clinical utility gene card for: von Hippel-Lindau (VHL)

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European Journal of Human Genetics - Clinical utility gene card for: von Hippel-Lindau (VHL)

Clinical Utility Gene Card

European Journal of Human Genetics advance online publication 28 August 2013; doi: 10.1038/ejhg.2013.180

Clinical utility gene card for: von Hippel–Lindau (VHL)

Jochen Decker¹, Christine Neuhaus², Fiona Macdonald³, Hiltrud Brauch⁴ and Eamonn R Maher^3,5

1. ¹Clinic III—Hematology and Oncology, Medical School of Johannes Gutenberg University, Mainz, Germany
2. ²Bioscientia, Center for Human Genetics, Ingelheim, Germany
3. ³Birmingham Women’s Hospital—West Midlands Regional Genetics Laboratory, Birmingham, UK
4. ⁴Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart and University Tuebingen, Tuebingen, Germany
5. ⁵Department of Medical Genetics, University of Cambridge, Cambridge, UK

Correspondence: Professor Dr J Decker, Clinic III—Hematology and Oncology, Medical School of Johannes Gutenberg University, Building 911 for Research and Development, Obere Zahlbacher Street 63, Mainz D 55131, Germany. Tel: +49 6131 277 94 51; Fax: +49 6131 277 94 52; E-mail: decker@uni-mainz.de

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1. Disease characteristics

1.1 Name of the disease (synonyms)

von Hippel–Lindau Syndrome (VHL).

1.2 OMIM# of the disease

193300.

1.3 Name of the analyzed genes or DNA/chromosome segments

VHL (3p25.3).¹

1.4 OMIM# of the gene(s)

(i) 608537 von Hippel–Lindau (VHL) and (ii) 168461 cyclin D1 gene (CCND1), a potential modifier of VHL.

1.5 Mutational spectrum

VHL mutations have been identified in all the three exons. About 30–60% are missense mutations, 20–40% large intragenic deletions (0.5–250 kb), 12–20% microdeletions or insertions and 7–11% nonsense mutations.^{2, 3, 4, 5} Genotype–phenotype correlations (see section 2.5 Positive clinical predictive value) have been described. Some hotspot/founder mutation have been reported.⁶ No mutations have been reported in the first 53 amino acids of pVHL.^{3, 5}

For the standard reference sequence in relation to the variants reported, a RefSeqGene record, for example, NCBI Reference Sequence: NM_000551.3, should be applied.

VHL gene variants can be found in the Human Gene Mutation Database. It is important for DNA diagnostics to share all new findings through this or similar databases.