RESUMO
Van der Woude syndrome (VWS) is a common form of syndromic cleft lip and palate and accounts for approximately 2% of all cleft lip and palate cases. Distinguishing characteristics include cleft lip with or without cleft palate, isolated cleft palate, bilateral lip pits, hypodontia, normal intelligence, and an autosomal-dominant mode of transmission with a high degree of penetrance. Previously, the VWS locus was mapped to a 1.6-cM region in 1q32-q41 between D1S491 and D1S205, and a 4.4-Mb contig of YAC clones of this region was constructed. In the current investigation, gene-based and anonymous STSs were developed from the existing physical map and were then used to construct a contig of sequence-ready bacterial clones across the entire VWS critical region. All STSs and BAC clones were shared with the Sanger Centre, which developed a contig of PAC clones over the same region. A subset of 11 clones from both contigs was selected for high-throughput sequence analysis across the approximately 1.1-Mb region; all but two of these clones have been sequenced completely. Over 900 kb of genomic sequence, including the 350-kb VWS critical region, were analyzed and revealed novel polymorphisms, including an 8-kb deletion/insertion, and revealed 4 known genes, 11 novel genes, 9 putative genes, and 3 psuedogenes. The positional candidates LAMB3, G0S2, HIRF6, and HSD11 were excluded as the VWS gene by mutation analysis. A preliminary gene map for the VWS critical region is as follows: [see text] 41-TEL. The data provided here will help lead to the identification of the VWS gene, and this study provides a model for how laboratories that have a regional interest in the human genome can contribute to the sequencing efforts of the entire human genome.
Assuntos
Cromossomos Humanos Par 1/genética , Fenda Labial/genética , Fissura Palatina/genética , Cistos/genética , Lábio , Polimorfismo Genético/genética , Animais , Mapeamento Cromossômico , Cromossomos Bacterianos/genética , Fenda Labial/patologia , Mapeamento de Sequências Contíguas , Análise Mutacional de DNA , DNA Bacteriano/genética , Humanos , Camundongos , Mapeamento Físico do Cromossomo , Ratos , SíndromeRESUMO
Branchio-oto-renal syndrome is an autosomal-dominant disorder with branchial, otologic, and renal manifestations. The branchial manifestations are usually inconsequential; however, the hearing impairment and renal malformations can be significant. Appropriate evaluation of affected persons is necessary to minimize disease morbidity.
Assuntos
Branquioma/patologia , Orelha/anormalidades , Rim/anormalidades , Pele/patologia , Síndrome , Audiometria de Tons Puros , Diagnóstico Diferencial , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/etiologia , Humanos , PrevalênciaRESUMO
Branchiootorenal syndrome is an autosomal dominant disorder that affects an estimated 2% of profoundly deaf children. In addition to hearing impairment, it is characterized by a lop-ear deformity, preauricular pits, branchial cleft sinus tracts, and renal anomalies. The pathogenesis of the disease remains unknown; however, the defective gene has been localized to chromosome 8q by family linkage studies.
