title: Refined mapping of a gene for autosomal dominant progressive sensorineural hearing loss (DFNA5) to a 2-cM region, and exclusion of a candidate gene that is expressed in the cochlea.
abstract: A gene for an autosomal dominant form of progressive sensorineural hearing loss (DFNA5) was previously assigned by us to a 15-cM region on chromosome 7p15. In this study, the DFNA5 candidate region was refined to less than 2 cM, and completely cloned in a YAC contig. The HOXA1 gene located in 7p15 was considered to be a good candidate gene for DFNA5 as it harbours mutations leading to developmental defects of the inner ear in mice. However, the refinement of the candidate region of DFNA5 excludes the HOXA1 gene as a candidate for DFNA5. We cloned a novel candidate gene (CG1, candidate gene 1), which is expressed in human fetal cochlea, from the DFNA5 candidate region. The complete cDNA sequence of CG1, encoding a 423 amino acid protein of unknown function, was determined. Mutation analysis of the CG1 gene in DFNA5 patients, however, could not reveal a disease-causing mutation.
authors.affiliation: Department of Medical Genetics, University of Antwerp, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Van Laer
authors.forename: G
authors.initials: G
authors.lastname: Van Camp
authors.forename: D
authors.initials: D
authors.lastname: van Zuijlen
authors.forename: E D
authors.initials: ED
authors.lastname: Green
authors.forename: M
authors.initials: M
authors.lastname: Verstreken
authors.forename: I
authors.initials: I
authors.lastname: Schatteman
authors.forename: P
authors.initials: P
authors.lastname: Van de Heyning
authors.forename: W
authors.initials: W
authors.lastname: Balemans
authors.forename: P
authors.initials: P
authors.lastname: Coucke
authors.forename: J H
authors.initials: JH
authors.lastname: Greinwald
authors.forename: R J
authors.initials: RJ
authors.lastname: Smith
authors.forename: E
authors.initials: E
authors.lastname: Huizing
authors.forename: P
authors.initials: P
authors.lastname: Willems
mesh_terms: D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D003001:Cloning, Molecular; D003051:Cochlea / Q000196:embryology; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015870:Gene Expression / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D011960:Receptors, Estrogen; D011995:Recombination, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA; D000094524:Gasdermins
chemical_list: D017931:DNA Primers; D005819:Genetic Markers; D011506:Proteins; D011960:Receptors, Estrogen; C111432:GSDME protein, human; D000094524:Gasdermins