Hearing impairment in Dutch patients with connexin 26 (GJB2) and connexin 30 (GJB6) mutations

Santos, Regie Lyn P.; Aulchenko, Yurii S.; Huygen, P.L.M.; Donk, Kim P. van der; Wijs, Ilse J. de; Kemperman, Martijn H; Admiraal, R.J.C.; Kremer, Hannie; Hoefsloot, Lies H.; Cremers, C.W.R.J.

doi:10.1016/j.ijporl.2004.08.015

Cited by 42 publications

(31 citation statements)

References 29 publications

(61 reference statements)

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“…Overall, the type of hearing impairment shown by the present DFNB7/11 family resembled the progressive type of hearing loss described in the 3 DFNA36 traits rather than the profound-to-severe type of hearing impairment that has been reported for the previously outlined DFNB7/11 traits. Generally, recessively inherited forms of hearing impairment are not progressive although, in addition to the DFNB7/11 family described here, also DFNB8, DFNB13, DFNB30, DFNB59, DFNB77 and several mutations in DFNB1 are reported to cause progressive hearing loss [Grillet et al, 2009;Janecke et al, 2002;Mustapha et al, 1998;Santos et al, 2005a;Schwander et al, 2007;Veske et al, 1996;Walsh et al, 2002]. Beside TMC1, also MYO3A (DFNB30), PJVK (DFNB59) and LOXHD1 (DFNB77) are expressed in hair cells, suggesting that intrinsic defects in hair cell function might be responsible for progressive recessive hearing loss [Grillet et al, 2009;Schwander et al, 2007;Walsh et al, 2002].…”

Section: Discussionmentioning

confidence: 74%

Progressive Sensorineural Hearing Loss and Normal Vestibular Function in a Dutch DFNB7/11 Family with a Novel Mutation in <i>TMC1</i>

Heer¹,

Collin

Huygen³

et al. 2010

Audiol Neurotol

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In a Dutch family with autosomal recessive hearing loss, genome-wide single-nucleotide polymorphism analysis mapped the genetic defect to the DFNB7/11 locus. A novel homozygous A-to-G change in the TMC1 gene was detected near the splice donor site of intron 19 (c.1763+3A→G) segregating with the hearing loss in this family. One of the 6 transmembrane domains and the actual TMC channel domain are predicted to be absent in the mutant protein. The sensorineural hearing impairment in this DFNB7/11 family has a postlingual onset. Audiometric analysis initially showed a steeply downward-sloping threshold configuration. The progressive phenotype in this family resembles the phenotype previously described for families with dominant TMC1 mutations (DFNA36) rather than that of families with recessive TMC1 mutations (DFNB7/11) which invariably cause severe-to-profound prelingual hearing impairment.

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Section: Discussionmentioning

confidence: 74%

Progressive Sensorineural Hearing Loss and Normal Vestibular Function in a Dutch DFNB7/11 Family with a Novel Mutation in <i>TMC1</i>

Heer¹,

Collin

Huygen³

et al. 2010

Audiol Neurotol

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“…This mutation has been found in other populations and is predicted to disrupt splicing, yielding no detectable mRNA (Santos, et al, 2005;Shahin, et al, 2002;Snoeckx, et al, 2005).…”

Section: Introductionmentioning

confidence: 94%

Prevalence of GJB2 (Connexin-26) and GJB6 (Connexin-30) Mutations in a Cohort of 300 Brazilian Hearing-Impaired Individuals: Implications for Diagnosis and Genetic Counseling

et al. 2009

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Objective: Hereditary nonsyndromic deafness is an autosomal recessive condition in about 80% of cases, and point mutations in the GJB2 gene (connexin 26) and two deletions in the GJB6 gene (connexin 30), del(GJB6-D13S1830) and del(GJB6-D13S1854), are reported to account for 50% of recessive deafness. Aiming at establishing the frequencies of GJB2 mutations and GJB6 deletions in the Brazilian population, we screened 300 unrelated individuals with hearing impairment, who were not affected by known deafness related syndromes. Methods:We firstly screened the most frequently reported mutations, c.35delG and c.167delT in the GJB2 gene, and del(GJB6-D13S1830) and del(GJB6-D13S1854) in the GJB6 gene, through specific techniques. The detected c.35delG and c.167delT mutations were validated by sequencing. Other mutations in the GJB2 gene were screened by single-strand conformation polymorphism and the coding region was sequenced when abnormal patterns were found.

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“…For the analysis of the GJB2, the entire region including non-coding exon1 were amplified by polymerase chain reaction (PCR) using the appropriate intronic primer sets reported previously [19,31]. For the study of GJB6 and SLC26A4 genes, all the exons including exon-intron bounderies of each gene were amplified by polymerase chain reaction (PCR) using the primer sets reported previously [24,32] and designed by Primer 3.0 software.…”

Section: Molecular Genetic Analysismentioning

confidence: 99%

“…Among the recessive mutations, 35delG is the most frequent in Caucasians, 167delT in Ashkenazi Jews, 235delC in East Asians, and R143W in Africans, suggesting the existence of founder effects in different ethnic groups [6][7][8][9][10][11][12][13][14][15][16][17][18]. In addition, some studies have shown the high prevalence of the IVS1 + 1G to A mutation in the non-coding part of the GJB2 gene [19,20].…”

Section: Introductionmentioning

confidence: 99%

Molecular analysis of the GJB2, GJB6 and SLC26A4 genes in Korean deafness patients

Lee

Choi

Bae

et al. 2008

International Journal of Pediatric Otorhinolaryngology

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Objective-Mutations in the GJB2, GJB6 and SLC26A4 genes are a frequent cause of hearing loss in a number of populations. However, little is known about the genetic causes of hearing loss in the Korean population.Methods-We sequenced the GJB2 and GJB6 genes to examine the role of mutations in these genes in twenty-two hearing loss patients. We also sequenced the SLC26A4 gene in seven patients with inner ear malformations, including enlarged vestibular aqueduct (EVA) revealed by computer tomography.Results-Coding sequence mutations in GJB2 were identified in 13.6% of the patients screened. Two different mutations, 235delC and T86R were found in three unrelated patients. The 235delC was the most prevalent mutation with an allele frequency of 6.9% in our patient group. No mutations, including 342 kb deletion, were found in GJB6 gene. Three different variants of SLC26A4 were identified in the EVA patients, including one novel mutation. Four EVA patients carried two mutant alleles of SLC26A4, and at least one allele in all patients was the H723R mutation, which accounted for 75% of all mutant alleles.Conclusions-Our results suggest that GJB2 and SLC26A4 mutations together make up a major cause of congenital hearing loss in the Korean population. Further studies may be able to identify other common variants that account for a significant fraction of hearing loss in the Korean population.

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Hearing impairment in Dutch patients with connexin 26 (GJB2) and connexin 30 (GJB6) mutations

Cited by 42 publications

References 29 publications

Progressive Sensorineural Hearing Loss and Normal Vestibular Function in a Dutch DFNB7/11 Family with a Novel Mutation in <i>TMC1</i>

Progressive Sensorineural Hearing Loss and Normal Vestibular Function in a Dutch DFNB7/11 Family with a Novel Mutation in <i>TMC1</i>

Prevalence of GJB2 (Connexin-26) and GJB6 (Connexin-30) Mutations in a Cohort of 300 Brazilian Hearing-Impaired Individuals: Implications for Diagnosis and Genetic Counseling

Molecular analysis of the GJB2, GJB6 and SLC26A4 genes in Korean deafness patients

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