Authors' recommendations: Hearing loss is an extremely common sensory disorder, diagnosed in 1 to 6 out of every 1000 children. It may be classified as sensorineural or conductive; congenital, prelingual, or postlingual; stable or progressive; and symmetric or asymmetric. It is also categorized by severity (mild, moderate, severe, or profound) and by audiometric configuration (flat, sloping, etc.). Finally, hearing loss is considered syndromic when it occurs in the context of multiple medical problems, or as nonsyndromic when no additional medical problems are present. Approximately 50% of congenital hearing loss is genetic in nature. Of those individuals with a genetic form of congenital hearing impairment, 30% are syndromic and 70% are nonsyndromic. Autosomal recessive forms of nonsyndromic hearing loss account for approximately 77% of cases, while autosomal dominant forms account for approximately 22%. The remaining cases of nonsyndromic hearing loss are due to X-linked gene variants or variants in the mitochondrial DNA. Numerous genetic loci have beenlinked to nonsyndromic hearing loss. Each locus is denoted by "DFN" for deafness, followed by "A" for a dominant inheritance, "B" for recessive inheritance, or no letter for X-linked inheritance. Subsequently, a unique number is used to distinguish the various loci. It is important to note that variants in some of the genes associated with nonsyndromic deafness can cause both recessive and dominant forms of hearing loss. Therefore, a specific gene or locus may be given both "DFNA" and "DFNB" labels. DFNB1 has been found to be the single most common cause of hereditary hearing loss. Variants involving the genes associated with the DFNB1 locus, the gap junction beta genes GJB2 and GJB6, are found in up to 50% of individuals with autosomal recessive, nonsyndromic, prelingual hearing loss. In addition, specific variants in the GJB2 gene are associated with DFNA3, an autosomal dominant form of nonsyndromic hearing impairment. GJB2 and GJB6, both of which are located on chromosome 13 at bands q11 to q12, encode connexin 26 and connexin 30, respectively. Connexins are integral membrane proteins that are a key component of gap junction channels. The GJB2 gene consists of two exons, the second of which contains the coding sequences for the connexin 26 protein. Most individuals with DFNB1 carry two variants within the GJB2 coding sequence. Some patients found to carry a single pathogenic variantwithin the GJB2 coding sequence are found to carry either a variant in the noncoding regions of GJB2 (such as the splice-site variant c.-3170G>A [c.IVS+1G>A]) or a deletion involving the neighboring GJB6 gene. It has previously been estimated that approximately 2% of DFNB1 patients carry one of two common GJB

Project Status: Completed

Year Published: 2010

URL for published report: http://www.hayesinc.com/hayes/crd/?crd=11183

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: HAYES, Inc.

Contact Address: 157 S. Broad Street, Suite 200, Lansdale, PA 19446, USA. Tel: 215 855 0615; Fax: 215 855 5218

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Contact Email: saleinfo@hayesinc.com

Copyright: 2010 Winifred S. Hayes, Inc