title: Bioinformatics analysis of candidate genes and mutations in a congenital sensorineural hearing loss pedigree: detection of 52 genes for the DFNA52 locus.
abstract: OBJECTIVE
  Previously, we have mapped the DFNA52 (Online Mendelian Inheritance in Man (OMIM) 607683) locus, using an 8.8-cM interval on the human chromosome 5q31.1-q32, in a large, consanguineous Chinese family with congenital sensorineural hearing loss. In order to identify the responsible pathogenic mutation within the DFNA52 locus, we set out to identify candidate disease genes within that region and to sequentially analyse these candidate genes.
  
  
  METHODS
  Using bioinformatics analysis, 52 candidate disease genes were identified based on gene expression data, deafness phenotype, and findings from a mouse model and from the literature (including two mouse deafness genes NEUROG1 and SMAD5). Mutation detection was performed for the 52 candidate genes, in patients from the pedigree.
  
  
  RESULTS
  In these patients, we found no disease-causing mutations in the coding and splice site regions of these genes, which segregated with the disease. However, 108 single nucleotide polymorphisms were identified, of which 15 were novel. Eleven of these 108 single nucleotide polymorphisms altered the encoded amino acid.
  
  
  CONCLUSIONS
  Although we identified a number of nucleotide changes in the affected patients, by analysis of coding and splice site regions of the genes, none of these changes are likely to be pathogenic mutations segregating with the disease. The result implies that the genes studied are unlikely to be a cause of DFNA52-linked sensorineural hearing loss.
authors.affiliation: National Laboratory of Medical Genetics of China, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Pan
authors.initials: P
authors.lastname: Qiong
authors.forename: Z
authors.initials: Z
authors.lastname: Hu
authors.forename: Y
authors.initials: Y
authors.lastname: Feng
authors.forename: Q
authors.initials: Q
authors.lastname: Pan
authors.forename: J
authors.initials: J
authors.lastname: Xia
authors.forename: K
authors.initials: K
authors.lastname: Xia
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D019295:Computational Biology; D004252:DNA Mutational Analysis; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D051379:Mice; D023421:Models, Animal; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: D002352:Carrier Proteins