title: A novel locus for autosomal dominant nonsyndromic hearing loss (DFNA44) maps to chromosome 3q28-29.
abstract: Hereditary non-syndromic sensorineural hearing loss (NSSHL) is a genetically highly heterogeneous group of disorders. Autosomal dominant forms account for up to 20% of cases. To date, 39 loci have been identified by linkage analysis of affected families that segregate NSSHL forms in the autosomal dominant mode (DFNA). Investigation of a large Spanish pedigree with autosomal dominant inheritance of bilateral and progressive NSSHL of postlingual onset excluded linkage to known DFNA loci and, in a subsequent genome-wide scan, the disorder locus was mapped to 3q28-29. A maximum two-point LOD score of 4.36 at theta=0 was obtained for marker D3S1601. Haplotype analysis placed the novel locus, DFNA44, within a 3-cM genetic interval defined by markers D3S1314 and D3S2418. Heteroduplex analysis and DNA sequencing of coding regions and exon/intron boundaries of two genes (CLDN16 and FGF12) in this interval did not reveal disease-causing mutations.
authors.affiliation: Unidad de Genética Molecular, Hospital Ramón y Cajal, Carretera de Colmenar Km 9, 28034, Madrid, Spain. fmoreno@hrc.insalud.es
authors.forename: Silvia
authors.initials: S
authors.lastname: Modamio-Høybjør
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Moreno-Pelayo
authors.forename: Angeles
authors.initials: A
authors.lastname: Mencía
authors.forename: Ignacio
authors.initials: I
authors.lastname: del Castillo
authors.forename: Sebastian
authors.initials: S
authors.lastname: Chardenoux
authors.forename: Daniel
authors.initials: D
authors.lastname: Armenta
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.forename: Christine
authors.initials: C
authors.lastname: Petit
authors.forename: Felipe
authors.initials: F
authors.lastname: Moreno
mesh_terms: D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D006239:Haplotypes; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D011995:Recombination, Genetic