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Bioinformatics analysis of candidate genes and mutations in a congenital sensorineural hearing loss pedigree: detection of 52 genes for the DFNA52 locus

Published online by Cambridge University Press:  29 February 2008

Pan Qiong ,
Z Hu ,
Y Feng ,
Q Pan ,
J Xia  and
K Xia
Pan Qiong
Affiliation:
National Laboratory of Medical Genetics of China, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China These authors contributed equally to this work
Z Hu
Affiliation:
National Laboratory of Medical Genetics of China, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China These authors contributed equally to this work
Y Feng*
Affiliation:
Department of Otorhinology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
Q Pan
Affiliation:
National Laboratory of Medical Genetics of China, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
J Xia
Affiliation:
National Laboratory of Medical Genetics of China, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
K Xia*
Affiliation:
National Laboratory of Medical Genetics of China, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
*
Address for correspondence: Dr Yong Feng, The Department of Otorhinology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, China. Fax: +86 731 4327469 E-mail: [email protected]
Dr Kun Xia, Central South University, National Laboratory of Medical Genetics of China, 110 Xiangya Road, Changsha, Hunan, China. Fax: +86 731 4478152 E-mail: [email protected]
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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.

Keywords

Sensorineural DeafnessDFNA ProteinGenetic Diseases
Type
Main Articles
Information
The Journal of Laryngology & Otology , Volume 122 , Issue 10 , October 2008 , pp. 1029 - 1036
Copyright
Copyright © JLO (1984) Limited 2008

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