TY - JOUR
T1 - Birt-Hogg-Dubé syndrome, a genodermatosis associated with spontaneous pneumothorax and kidney neoplasia, maps to chromosome 17p11.2
AU - Schmidt, Laura S.
AU - Warren, Michelle B.
AU - Nickerson, Michael L.
AU - Weirich, Gregor
AU - Matrosova, Vera
AU - Toro, Jorge R.
AU - Turner, Maria L.
AU - Duray, Paul
AU - Merino, Maria
AU - Hewitt, Stephen
AU - Pavlovich, Christian P.
AU - Glenn, Gladys
AU - Greenberg, Cheryl R.
AU - Linehan, W. Marston
AU - Zbar, Berton
N1 - Funding Information:
We thank the familie for their cooperation. We thank Alejandro Schäffer (National Center for Biotechnology Information, National Library of Medicine, NIH) and James Tomlin (Center for Information Technology, Computational Bioscience and Engineering Lab, Bioinformatics and Molecular Analysis Section, NIH) for running the multipoint linkage computations. We thank Michele Moody for expert technical assistance. This publication has been funded in whole or in part by Federal funds from the National Cancer Institute, NIH, under contract N01-C0-56000. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
PY - 2001
Y1 - 2001
N2 - Birt-Hogg-Dubé 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 nonrecombination 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 chromosomal band 17p11.2, a genomic region that, because of the presence of low-copy-number repeat elements, is unstable and that is associated with a number of diseases. Identification of the gene for BHD may reveal a new genetic locus responsible for renal neoplasia and for lung and hair-follicle developmental defects.
AB - Birt-Hogg-Dubé 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 nonrecombination 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 chromosomal band 17p11.2, a genomic region that, because of the presence of low-copy-number repeat elements, is unstable and that is associated with a number of diseases. Identification of the gene for BHD may reveal a new genetic locus responsible for renal neoplasia and for lung and hair-follicle developmental defects.
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U2 - 10.1086/323744
DO - 10.1086/323744
M3 - Article
C2 - 11533913
AN - SCOPUS:0034821623
SN - 0002-9297
VL - 69
SP - 876
EP - 882
JO - American journal of human genetics
JF - American journal of human genetics
IS - 4
ER -