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Exclusion of PTEN, CTNNB1, and PTCH as candidate genes for Birt-Hogg-Dube syndrome
  1. J R Toro1,2,
  2. Y O Shevchenko2,
  3. J G Compton2,
  4. S J Bale2
  1. 1National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland, USA
  2. 2Genetic Studies Section, Laboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland, USA
  1. Correspondence to:
 Dr J R Toro, National Institutes of Health, Building 10, Room 12N-238, 10 Center Drive, MSC 1908, Bethesda, Maryland 20892-1908, USA;
 torojo{at}exchange.nih.gov

https://doi.org/10.1136/jmg.39.2.e10

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    In 1977, Birt, Hogg, and Dube described a kindred in which 15 of 70 members over three generations exhibited multiple, small, grey skin coloured, dome shaped papules distributed over the face, neck, and upper trunk inherited in an autosomal dominant pattern.1 Histological examination of these lesions showed fibrofolliculomas, trichodiscomas, and acrochordons. This triad has become known as Birt-Hogg-Dube (BHD) syndrome. Since the initial report, other cases have been described.2–13

    The cutaneous manifestations of BHD, which typically appear during the third or fourth decade of life, have been associated with renal carcinoma,2,5 spontaneous pneumothorax,2,6 and colonic polyps.3,4 Toro et al2 recently reported three extended kindreds in whom renal neoplasms and BHD segregated together. Two kindreds had renal oncocytomas and a third had a variant of papillary renal cell carcinoma. Renal neoplasms can be familial or sporadic. Four types of familial renal neoplasms have been well described: (1) clear cell renal carcinoma associated with haemangioblastomas of the brain, spine, and eye owing to mutations in the von Hippel-Lindau (VHL) disease tumour suppressor gene,4 (2) clear cell renal carcinoma associated with constitutional, balanced translocations involving the short arm of chromosome 3,15–17 (3) papillary renal cell carcinoma associated with germline mutations in the tyrosine kinase domain of the MET proto-oncogene,18 and (4) renal oncocytoma.19

    In this study, we report an extended family that we evaluated for PTEN, CTNNB1, and PTCH as candidate genes for BHD and renal cancer. These genes were selected for study because mutations in each are associated with a disorder that has clinical features that overlap BHD and because each of these disorders carries an increased risk for internal malignancy. We used a candidate gene approach. We first performed sequencing analysis, but no mutations …

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