BHDS map to 17p11.2.pdf

Am. J. Hum. Genet. 69:876–882, 2001 876 Report Birt-Hogg-Dube? Syndrome, a Genodermatosis Associated with Spontaneous Pneumothorax and Kidney Neoplasia, Maps to Chromosome 17p11.2 Laura S. Schmidt,1 Michelle B. Warren,1 Michael L. Nickerson,2 Gregor Weirich,7 Vera Matrosova,2 Jorge R. Toro,4 Maria L. Turner,3 Paul Duray,5 Maria Merino,5 Stephen Hewitt,5 Christian P. Pavlovich,6 Gladys Glenn,4 Cheryl R. Greenberg,8 W. Marston Linehan,6 and Berton Zbar2 1Intramural Research Support Program, SAIC, and 2Laboratory of Immunobiology, National Cancer Institute–Frederick, Frederick, MD; 3Dermatology Branch, 4Genetic Epidemiology Branch, 5Laboratory of Pathology, and 6Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda; 7Technische Universita?t Mu?nchen, Institut fu?r Pathologie, Munich; and 8Department of Pediatrics and Child Health Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg Birt-Hogg-Dube? syndrome (BHD), an inherited autosomal genodermatosis characterized by benign tumors of the hair follicle, has been associated with renal neoplasia, lung cysts, and spontaneous pneumothorax. To identify the BHD locus, we recruited families with cutaneous lesions and associated phenotypic features of the BHD syndrome. We performed a genomewide scan in one large kindred with BHD and, by linkage analysis, localized the gene locus to the pericentromeric region of chromosome 17p, with a LOD score of 4.98 at D17S740 (recombination fraction 0). Two-point linkage analysis of eight additional families with BHD produced a maximum LOD score of 16.06 at D17S2196. Haplotype analysis identified critical recombinants and defined the minimal region of nonrecom- bination as being within a !4-cM distance between D17S1857 and D17S805. One additional family, which had histologically proved fibrofolliculomas, did not show evidence of linkage to chromosome 17p, suggesting genetic heterogeneity for BHD. The BHD locus lies within c