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RESEARCH PRODUCT

Epidemiological study of nonsyndromic hearing loss in Sicilian newborns

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description

Deafness is caused by a variety of facts, genetic and environmental. Regarding the acquired causes, deafness can be the consequence of prenatal infections, acoustic or cerebral trauma, and the use of ototoxic drugs. Deafness can be the only manifestation (nonsyndromic forms) or it may occur together with other phenotypic findings (syndromic forms). The majority of nonsyndromicdeafness has a genetic basis [Van Camp et al., 1997]. In recent years, deafness and hearing loss have assumed a clinical importance in the study of congenital disorders [Morton et al., 1991]. The clinical interest for hearing loss is supported by the social impact that this disorder has; if not treated, delays in the development of language and learning skills will occur [Yoshinaga-Itano et al., 1998]. In the absence of newborn screening, hearing loss might not be noticed by parents, teachers or paediatricians until the child begins to have difficulties at speaking and learning, sometimes as late as age 2 or 3 years. In genetic nonsyndromic hearing loss (NSHL) the inheritance pattern is autosomal recessive (80%), autosomal dominant (17%), X-linked (2–3%), and mitochondrial (<1%) [Snoeckx et al., 2005]. Overall NSHL is very heterogeneous; about 100 loci have been related to NSHL and 37 genes encode for proteins which have a role in inner ear physiology [Snoeckx et al., 2005].However, variants of one gene, GJB2 (gap junction protein, beta 2, OMIM#220290) account for up of 50% of NSHL in many populations [Kenneson et al., 2002]. TheGJB2 gene is expressed in a variety of cells and tissues. It encodes connexin 26 protein (CX26), one member of a great number proteins family which are involved in the formation of the splice gap (gap-junctions) that allow the direct transfer of small ionic molecules between adjacent cells. In the cochleaCX26-containing gap junctions areproposed to maintain Kþ homeostasis between outer hair cells and endolymphatic space during the auditory transduction [Wangemann, 2002]. Recently, it has been know that the intracellular transduction of second messenger inositol triphosphate (IP3) is also essential for the perception of sound [Beltramello et al., 2005]. The GJB2 gene is localized on chromosome 13 (13q11-q12) [Guilford et al., 1994], and it contains two exons with only the second is translated [Griffith et al., 2000]. Many NSHL-causing mutations of GJB2 have been reported [Murgia et al., 1999] and they have been stored in world wide gene mutations database http:// www.crs.es/deafness. Based on published data, these GJB2 variant have been classified as truncating and nontruncating mutations [Snoeckx et al., 2005]. The group of truncating contains nonsense mutations, deletions, insertions, and duplications that create an anticipated stop codon; the splice site mutation (IVS1þ 1 G!A) is classified as truncating [Snoeckx et al., 2005]. The group of nontruncating contains amino acid substitutions and one in frame deletion [Snoeckx et al., 2005] which could have severe phenotypic consequences because for some amino acid substitutions, CX26 function could be lost. The most common truncating mutations are the small deletions 35delG, 167delT, 235delC [Snoeckx et al., 2005], the splice site mutation IVS1þ 1 G!A [Denoyelle et al., 1999] however, the prevalence