title: Second family with hearing impairment linked to 19q13 and refined DFNA4 localisation.
abstract: Until now, over 30 loci have been identified by linkage analysis of affected families that segregate non-syndromic and dominantly inherited forms of hearing impairment (DFNA). A German family with a non-syndromic progressive hearing impairment transmitted in autosomal dominant mode was linked to 19q13.3-q13.4 by a genome-wide scan. Due to the low lod-score (1.85 at theta=0.05) for APOC2-locus we extended the fine mapping attempt with further markers in the same chromosomal region. This resulted in significant evidence for linkage to the markers D19S246 and D19S553 (two-point lod-score of 4.05 and 3.55 at theta=0.0) and a candidate critical region of 14 cM between markers D19S412 and D19S571. This region shows partial overlap with the previously reported DFNA4 critical region. The human gene BAX is orthologous to the rodent Bcl2-related apoptosis gene that is temporally expressed during the postnatal period in the developing inner ear of the mouse. BAX, mapping at a distance of no more than 0.73 cM distally to marker D19S553 appeared a likely candidate in our pedigree but genomic sequencing of coding regions and exon/intron boundaries excluded disease-related mutations. However, additional ESTs in the same region remain to be tested.
authors.affiliation: Hals-Nasen-Ohren-Klinik, Tübingen, Germany.
authors.forename: Farhad
authors.initials: F
authors.lastname: Mirghomizadeh
authors.forename: Bettina
authors.initials: B
authors.lastname: Bardtke
authors.forename: Marcella
authors.initials: M
authors.lastname: Devoto
authors.forename: Markus
authors.initials: M
authors.lastname: Pfister
authors.forename: Jens
authors.initials: J
authors.lastname: Oeken
authors.forename: Elke
authors.initials: E
authors.lastname: König
authors.forename: Emilia
authors.initials: E
authors.lastname: Vitale
authors.forename: Antonio
authors.initials: A
authors.lastname: Riccio
authors.forename: Assunta
authors.initials: A
authors.lastname: De Rienzo
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Zenner
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Blin
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D008126:Lod Score; D018995:Myosin Heavy Chains; D024462:Myosin Type II; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein
chemical_list: D002352:Carrier Proteins; D018995:Myosin Heavy Chains; D024462:Myosin Type II; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human; C477830:MYH7b protein, human