Document Detail

A comprehensive network and pathway analysis of human deafness genes.
MedLine Citation:
PMID:  23770690     Owner:  NLM     Status:  In-Data-Review    
OBJECTIVE: To perform comprehensive network and pathway analyses of the genes known to cause genetic hearing loss.
STUDY DESIGN: In silico analysis of deafness genes using ingenuity pathway analysis (IPA).
METHODS: Genes relevant for hearing and deafness were identified through PubMed literature searches and the Hereditary Hearing Loss Homepage. The genes were assembled into 3 groups: 63 genes that cause nonsyndromic deafness, 107 genes that cause nonsyndromic or syndromic sensorineural deafness, and 112 genes associated with otic capsule development and malformations. Each group of genes was analyzed using IPA to discover the most interconnected, that is, "nodal" molecules, within the most statistically significant networks (p < 10).
RESULTS: The number of networks that met our criterion for significance was 1 for Group 1 and 2 for Groups 2 and 3. Nodal molecules of these networks were as follows: transforming growth factor beta1 (TGFB1) for Group 1, MAPK3/MAPK1 MAP kinase (ERK 1/2) and the G protein coupled receptors (GPCR) for Group 2, and TGFB1 and hepatocyte nuclear factor 4 alpha (HNF4A) for Group 3. The nodal molecules included not only those known to be associated with deafness (GPCR), or with predisposition to otosclerosis (TGFB1), but also novel genes that have not been described in the cochlea (HNF4A) and signaling kinases (ERK 1/2).
CONCLUSION: A number of molecules that are likely to be key mediators of genetic hearing loss were identified through three different network and pathway analyses. The molecules included new candidate genes for deafness. Therapies targeting these molecules may be useful to treat deafness.
Georgios A Stamatiou; Konstantina M Stankovic
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology     Volume:  34     ISSN:  1537-4505     ISO Abbreviation:  Otol. Neurotol.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100961504     Medline TA:  Otol Neurotol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  961-70     Citation Subset:  IM    
*Department of Otolaryngology, Hippokration General Hospital, University of Athens, Athens, Greece; and †Department of Otology and Laryngology, Harvard Medical School and Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, U.S.A.
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