title: Mapping of a new autosomal dominant non-syndromic hearing loss locus (DFNA43) to chromosome 2p12.
abstract: Hearing impairment (HI) is the most frequent sensory defect with wide genetic heterogeneity. Approximately 80% of genetic hearing loss is non-syndromic and 15-25% of exhibit autosomal dominant inheritance. We analysed an Italian three generation family in which non-syndromic hearing impairment is transmitted as an autosomal dominant trait. Onset of HI in all affected subjects occurred in the second decade of life, with subsequent gradual progression from moderate to profound loss. HI was bilateral and symmetrical, involving all frequencies. After exclusion of the known DFNA loci with markers from the Hereditary Hearing Loss Homepage (URL: http://dnalab-www.uia.ac.be/dnalab/hhh), a genome wide scan was carried out using 358 highly informative microsatellite markers. Significant linkage (Zmax=4.21, theta=0) was obtained with chromosome 2p12 markers. The results were confirmed by multipoint analysis (Zmax=4.51), using the location score method. Haplotype analysis defined a 9.6 cM disease gene interval on chromosome 2 without overlap with the other identified loci. Fine mapping and identification of candidate genes are in progress.
authors.affiliation: IRCCS, S Giovanni Rotondo CCS-Mendel Institute, Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Flex
authors.forename: M
authors.initials: M
authors.lastname: Mangino
authors.forename: M
authors.initials: M
authors.lastname: Mazzoli
authors.forename: A
authors.initials: A
authors.lastname: Martini
authors.forename: V
authors.initials: V
authors.lastname: Migliosi
authors.forename: A
authors.initials: A
authors.lastname: Colosimo
authors.forename: R
authors.initials: R
authors.lastname: Mingarelli
authors.forename: A
authors.initials: A
authors.lastname: Pizzuti
authors.forename: B
authors.initials: B
authors.lastname: Dallapiccola
mesh_terms: D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007558:Italy; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D051178:alpha Catenin
chemical_list: C495273:CTNNA1 protein, human; D003598:Cytoskeletal Proteins; D051178:alpha Catenin; D004247:DNA