Clinical Studies of Families With Hearing Loss Attributable to Mutations in the Connexin 26 Gene (GJB2/DFNB1)

Cohn, Edward S.; Kelley, Philip M.; Fowler, Trent; Gorga, Michael P.; Lefkowitz, David M.; Kuehn, H J; Schaefer, Gerald; Gobar, Lisa S.; Hahn, Francis J.; Harris, David J.; Kimberling, William J.

doi:10.1542/peds.103.3.546

Cited by 203 publications

(178 citation statements)

References 14 publications

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“…In patients who were homozygous or heterozygous for 35delG, the moderate-severe degrees of hearing loss were predominant, a pattern that is in agreement with the literature 17,38,39 . Patients who are homozygous for 35delG display a large variability in the degrees of hearing loss.…”

Section: Ic -Index Cases; Hl -Hearing Losssupporting

confidence: 90%

“…As protein Cx26 is involved in the ion homeostasis of the inner ear, some of these patients may be capable of hearing, for they present a moderate hearing loss, suggesting the existence of alternative or compensatory homeostatic mechanisms. Alterations in protein Cx26 can adversely affect the development of the hearing system, resulting in variations of the degree of hearing loss or assymmetry 38 . Environmental influences, such as noises and ototoxic drugs, can be additive or synergists to the defects caused by mutations in the GJB2 gene, thus increasing the hearing loss 17,38,41 .…”

Section: Ic -Index Cases; Hl -Hearing Lossmentioning

confidence: 99%

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Correlação entre dados audiométricos e mutação 35delG em dez pacientes

Piatto

Moreira

Silva

et al. 2007

Rev. Bras. Otorrinolaringol.

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Mutações no gene da conexina 26 parecem ser extremamente comuns na gênese da surdez hereditária não-sindrômica, especialmente, a mutação 35delG, mas ainda há poucos estudos que descrevem as características audiométricas dos pacientes portadores dessas mutações. OBJETIVO: Analisar as características audiométricas em pacientes com mutações no gene da conexina 26 para se delinear uma correlação genótipo-fenótipo. CASUÍSTICA E MÉTODO: Foram avaliadas audiometrias tonal de 33 casos-índice com surdez sensorioneural não-sindrômica e de 8 familiares afetados. Testes moleculares específicos foram realizados para analisar mutações no gene da conexina 26. FORMA DE ESTUDO: Estudo de casos, retrospectivo, em corte transversal. RESULTADOS: Foram encontradas as prevalências de 27,3% da mutação 35delG nos casos-índice e de 12,5% nos familiares afetados. Em relação aos graus de perda, foram encontrados, 41,5% dos pacientes com grau profundo, 39,0% com grau grave e 19,5% com grau moderado com, os pacientes homozigotos e heterozigotos para 35delG, predominando nos graus moderado-grave. CONCLUSÃO: Estes resultados sugerem que os dados audiométricos, associados ao diagnóstico molecular para a surdez, permitiram delinear uma correlação genótipo-fenótipo em dez pacientes com a mutação 35delG. Mas é necessário estudo multicêntrico para se verificar a real expressão fenotípica na população brasileira relacionada à mutação 35delG.

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Section: Ic -Index Cases; Hl -Hearing Losssupporting

confidence: 90%

Section: Ic -Index Cases; Hl -Hearing Lossmentioning

confidence: 99%

Correlação entre dados audiométricos e mutação 35delG em dez pacientes

Piatto

Moreira

Silva

et al. 2007

Rev. Bras. Otorrinolaringol.

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“…The 35delG mutation is the most common mutation of GJB2 within this ethnic group [Denoyelle et al, 1997; Zelante Estivill et al, 1998]. Individuals with GJB2-related hearing loss are not at increased risk of additional health problems such as vision difficulties and mental retardation [Cohn et al, 1999]. Recent studies have suggested that infants with GJB2-related hearing loss might benefit from early cochlear implantation [Green et al, 2002].…”

Section: Discussionmentioning

confidence: 99%

“…To date, 79 loci for nonsyndromic hearing loss have been identified: 40 autosomal dominant, 34 autosomal recessive, and 5 X-linked [Hereditary Hearing Loss Homepage, 2003]. Multiple studies have shown that mutations in the single GJB2 gene may account for up to 50% of nonsyndromic sensorineural autosomal recessive hearing loss or 20% of all childhood hearing loss [Denoyelle et al, 1997;Zelante et al, 1997;Cohn et al, 1999;Green et al, 2002]. The GJB2 gene encodes the connexin 26 protein, which is involved in gap junction formation allowing cell-to-cell diffusion and the transfer of ions between neighboring cells.…”

Section: Introductionmentioning

confidence: 99%

Methodology of a multistate study of congenital hearing loss: Preliminary data from Utah newborn screening

Dent

Kenneson

Palumbos

et al. 2004

American J of Med Genetics Pt C

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A multistate Centers for Disease Control and Prevention (CDC) study was designed to investigate the etiology of congenital hearing loss in infants ascertained through state-mandated hearing screening or early hearing loss detection and intervention (EHDI) programs. At least 50% of permanent childhood-onset hearing loss is due to genetic causes, and approximately 20% of all infants with congenital hearing loss have mutations in the GJB2 gene. Another 1% of childhood hearing loss is due to mitochondrial DNA (mtDNA) mutations. The specific aims of this study are to 1) classify the etiology of congenital hearing loss in infants by doing prospective genetic evaluations of all newborns with permanent hearing loss from defined geographic areas, 2) determine the frequency of mutations in GJB2 and two common mitochondrial mutations in these populations, and 3) establish a model infrastructure linking genetic services to statewide EHDI programs. As of April 2003, Utah is the only center evaluating patients. Study subjects identified through the Utah Department of Health EHDI program are contacted by letter and offered a comprehensive medical genetics evaluation with DNA testing for GJB2 and mitochondrial mutations A1555G and A7445G. To date, 25 probands and their immediate family members have been evaluated. We have identified 20 cases with nonsyndromic hearing loss (7 multiplex and 13 simplex), 4 with syndromic hearing loss, and 1 with presumed cytomegalovirus (CMV)-induced hearing loss. Six of 19 (32%) nonsyndromic cases with sensorineural hearing loss have mutations of one or both alleles of the GJB2 gene, and 21% are homozygous or compound heterozygotes for the 35delG mutation. No A1555G or A7445G mtDNA mutations have been found. Data reported to date include only children born in Utah, but EHDI programs in Hawaii, Rhode Island, and designated areas of Georgia have begun enrolling children in what is now a multistate collaborative study. This is the first comprehensive investigation to determine the etiology of hearing loss from populations ascertained through EHDI programs. The results of this study will facilitate the incorporation of genetic services into EHDI programs. ß

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“…It is clear that genetic testing to determine the cause of deafness facilitates prediction of the course of hearing loss and prognostication of language development. There is, however, some controversy regarding genotype/phenotype correlation (Cohn et al 1999;Cryns et al 2004;Denoyelle et al 1999;Estivill et al 1998;Murgia et al 1999;Orzan et al 1999). For example, prediction of the degree of hearing loss was difficult, and environmental factors as well as modifier genes may have been involved (Cohn et al 1999;Murgia et al 1999;Orzan et al 1999).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2005

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Mutations in the GJB2 (connexin 26, Cx26) gene are the major cause of nonsyndromic hearing impairment in many populations. Genetic testing offers opportunities to determine the cause of deafness and predict the course of hearing, enabling the prognostication of language development. In the current study, we compared severity of hearing impairment in 60 patients associated with biallelic GJB2 mutations and assessed the correlation of genotypes and phenotypes. Within a spectrum of GJB2 mutations found in the Japanese population, the phenotype of the most prevalent mutation, 235delC, was found to show more severe hearing impairment than that of V37I, which is the second most frequent mutation. The results of the present study, taken together with phenotypes caused by other types of mutations, support the general rule that phenotypes caused by the truncating GJB2 mutations are more severe than those caused by missense mutations. The present in vitro study further confirmed that differences in phenotypes could be explained by the protein expression pattern.

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Clinical Studies of Families With Hearing Loss Attributable to Mutations in the Connexin 26 Gene (GJB2/DFNB1)

Abstract: Newborns with confirmed hearing loss should have Cx26 testing. Cx26 testing will help define a group in which approximately 60% will have profound or severe-profound hearing loss and require aggressive language intervention (many of these patients will be candidates for cochlear implants).

Cited by 203 publications

References 14 publications

Correlação entre dados audiométricos e mutação 35delG em dez pacientes

Correlação entre dados audiométricos e mutação 35delG em dez pacientes

Methodology of a multistate study of congenital hearing loss: Preliminary data from Utah newborn screening

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

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