Carrier Rates in the Midwestern United States for <EMPH TYPE="ITAL">GJB2</EMPH> Mutations Causing Inherited Deafness

Abstract

Our data suggest that mutations in GJB2 are the leading cause of moderate-to-profound congenital inherited deafness in the midwestern United States. Screening of the GJB2 mutation can be offered to individuals with congenital deafness with high sensitivity and specificity by screening only for the 35delG mutation. A positive finding should establish an etiologic diagnosis and affect genetic counseling.

Clinical features of patients with GJB2 (connexin 26) mutations: severity of hearing loss is correlated with genotypes and protein expression patterns

“…Note that patients associated with 235delC show relatively severer hearing loss whereas V37I-involved patients show a relatively mild phenotype. It is also evident that patients associated with inactivating mutation/inactivating mutation showed a severer phenotype than patients with noninactivating mutation/ noninactivating mutation 35delG exhibit severe-to-profound hearing impairment (Cohn et al 1999;Cryns et al 2004;Denoyelle et al 1997Denoyelle et al , 1999Green et al 1999;Marlin et al 2001;Wilcox et al 2000). The status of the 235delC mutation, which seems to be a unique mutation in populations with Asian ancestry, is comparable to the 35delG mutation in Caucasoid populations.…”

Infrequency of two deletion mutations at the DFNB1 locus in patients and controls

“…Although some hearing impaired patients would be expected to be GJB2 carriers by chance, the cumulative data support the existence of additional, as yet unknown, mutations at the DFNB1 locus. Alternatively, it is possible that carriers of recessive mutations in GJB2 are at an increased risk for hearing loss from other causes [Estivill et al, 1998;Green et al, 1999;Roux et al, 2004;Tang et al, 2006;Putcha et al, 2007]. The observations of this and prior studies suggest that further investigation of the DFNB1 locus is needed.…”

“…It is curious that prior studies have consistently demonstrated larger than expected numbers of heterozygous GJB2 mutation carriers in patient cohorts [Estivill et al, 1998;Green et al, 1999;Roux et al, 2004;Hutchin et al, 2005;Tang et al, 2006;Putcha et al, 2007]. Although some hearing impaired patients would be expected to be GJB2 carriers by chance, the cumulative data support the existence of additional, as yet unknown, mutations at the DFNB1 locus.…”

Interação entre audiologia e genética no estudo de uma família: a complexidade do diagnóstico molecular e do aconselhamento genético

“…The thorough audiological examination performed with the core of the family (parents and siblings) added to the tests done with the half-sister and the nephews revealed that the three siblings had practically the same kind of hearing loss, and that their parents, sister, half-sister and nephews had normal hearing [3][4][5][6][7][8][9][10][11] .…”

“…Behavioral and electrophysiological tests are available to assist with the audiological diagnosis, and may be used as part of the assessment procedure [3][4][5][6][7][8][9][10][11] . Test applicability is based on patient maturation and development status.…”