Prevalence and nature of connexin 26 mutations in children with non‐syndromic deafness

Dahl, Hans‐Henrik M.; Saunders, Kerryn; Kelly, Therese; Osborn, Amelia H.; Wilcox, Stephen; Cone‐Wesson, Barbara; Wunderlich, Julia; Sart, Desirée du; Kamarinos, Maria; Gardner, R. J McKinlay; Dennehy, Shirley; Williamson, Robert; Vallance, Neil; Mutton, Patricia

doi:10.5694/j.1326-5377.2001.tb143093.x

Cited by 35 publications

(29 citation statements)

References 18 publications

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“…This mutation was previously reported in Australian and Indian populations (Dahl et al 2001; Mani et al 2009) and was shown to impair trafficking of the protein to the plasma membrane. Given the shared ancestral history of Pakistan and India, it is tempting to speculate that p.I35S may be another ancestral mutation in the subcontinent.…”

Section: Discussionsupporting

confidence: 54%

Contribution of GJB2 Mutations to Hearing Loss in the Hazara Division of Pakistan

2013

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Mutations of GJB2, which encodes connexin 26, are the most common cause of hereditary hearing loss in many human populations. This study was initiated to determine the prevalence of GJB2 mutations in individuals with hearing loss from the Hazara Division in Pakistan. We recruited 70 participants with nonsyndromic deafness segregating as an apparently recessive trait and directly sequenced the GJB2 coding region from their DNA. The homozygous mutations c.71 G→A (p.W24X), c.104 T→G (p.I35S), and c.35delG (p.G12VfsX1) were identified as the cause of hearing loss in three participants (4.28%); in populations from other areas of Pakistan, frequencies of 6–7% have been observed. The mutations c.104 T→G and c.35delG were identified in Pakistan for the first time. These results confirm the low prevalence of GJB2 mutations in Hazara and suggest that mutations in other genes may play a significant role in the etiology of deafness in this population.

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Section: Discussionsupporting

confidence: 54%

Contribution of GJB2 Mutations to Hearing Loss in the Hazara Division of Pakistan

2013

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“…The pathogenic effect of these single mutations are uncertain, but we have attributed the hearing losses to thise GJB2 gene changes, because the proportion of children with hearing loss and one detectable recessive GJB2 mutation is significantly higher than that of the general population (approximately 1%) [29]. The pathogenic effects of a number of other changes in the GJB2 gene of 24 children are also ambiguous.…”

Section: Discussionmentioning

confidence: 99%

Etiology and Audiological Outcomes at 3 Years for 364 Children in Australia

et al. 2013

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Hearing loss is an etiologically heterogeneous trait with differences in the age of onset, severity and site of lesion. It is caused by a combination of genetic and/or environmental factors. A longitudinal study to examine the efficacy of early intervention for improving child outcomes is ongoing in Australia. To determine the cause of hearing loss in these children we undertook molecular testing of perinatal “Guthrie” blood spots of children whose hearing loss was either detected via newborn hearing screening or detected later in infancy. We analyzed the GJB2 and SLC26A4 genes for the presence of mutations, screened for the mitochondrial DNA (mtDNA) A1555G mutation, and screened for congenital CMV infection in DNA isolated from dried newborn blood spots. Results were obtained from 364 children. We established etiology for 60% of children. One or two known GJB2 mutations were present in 82 children. Twenty-four children had one or two known SLC26A4 mutations. GJB2 or SLC26A4 changes with unknown consequences on hearing were found in 32 children. The A1555G mutation was found in one child, and CMV infection was detected in 28 children. Auditory neuropathy spectrum disorder was confirmed in 26 children whose DNA evaluations were negative. A secondary objective was to investigate the relationship between etiology and audiological outcomes over the first 3 years of life. Regression analysis was used to investigate the relationship between hearing levels and etiology. Data analysis does not support the existence of differential effects of etiology on degree of hearing loss or on progressiveness of hearing loss.

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“…This is within the expected range, as the 35delG carrier frequency in the Australian population has previously been estimated to be 1:100 and the overall prevalence of carriers of connexin 26 mutations to be 1:50. 10 The V37I amino acid substitution was found as a single change in two cases (one Asian and one ''more than one race''). No other GJB2 or GJB6 mutations were detected in these two children.…”

Section: Discussionmentioning

confidence: 99%

“…Although two biallelic GJB2 mutations were found in 34 of these children, 18 (35%) had a detectable mutation in only one allele. 10 This number is too high to represent carriers of GJB2 mutations with another cause of deafness. Therefore, it was concluded that the GJB2 mutations in many of these 18 children might be associated with the hearing loss.…”

Section: Discussionmentioning

confidence: 99%

“…We have estimated that mutations in the GJB2 gene account for the hearing loss in approximately 10-15% of Australians with moderate, severe and profound prelingual non-syndromic deafness. 10 Unlike more severe forms of hearing loss, slight or mild SNHL is often not detected in children or, if detected, rarely investigated in detail. Most GJB2 mutations that have been reported have therefore been mainly associated with more severe hearing losses, 11 and their role in milder losses remains unknown.…”

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The contribution of GJB2 mutations to slight or mild hearing loss in Australian elementary school children

Dahl

Tobin

Poulakis

et al. 2006

Journal of Medical Genetics

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Background: There is a lack of information on prevalence, cause and consequences of slight/mild bilateral sensorineural hearing loss (SNHL) in children. We report the first systematic genetic analysis of the GJB2 gene in a population-derived sample of children with slight/mild bilateral SNHL. Methods: Hearing tests were conducted in 6240 Australian elementary school children in Grades 1 and 5. 55 children (0.88%) were found to have a slight/mild sensorineural hearing loss. 48 children with slight/mild sensorineural hearing loss and a matched group of 90 children with normal hearing participated in a genetic study investigating mutations in the GJB2 gene, coding for connexin 26, and the presence of the del(GJB6-D13S1830) and del(GJB6-D13S1854) deletions in the GJB6 gene, coding for connexin 30. Results: Four of 48 children with slight/mild sensorineural hearing loss were homozygous for the GJB2 V37I change. The four children with homozygous V37I mutations were all of Asian background and analysis of SNPs in or near the GJB2 gene suggests that the V37I mutation arose from a single mutational event in the Asian population. Discussion: Based on the prevalence of carriers of this change we conclude that V37I can be a causative mutation that is often associated with slight/mild sensorineural hearing loss. No other children in the slight/mild hearing loss group had a hearing loss related to a GJB2 mutation. One child with normal hearing was homozygous for the R127H change and we conclude that this change does not cause hearing loss. Two children of Asian background were carriers of the V37I mutation. Our data indicate that slight/ mild sensorineural hearing loss due to the GJB2 V37I mutation is common in people of Asian background.

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Prevalence and nature of connexin 26 mutations in children with non‐syndromic deafness

Cited by 35 publications

References 18 publications

Contribution of GJB2 Mutations to Hearing Loss in the Hazara Division of Pakistan

Contribution of GJB2 Mutations to Hearing Loss in the Hazara Division of Pakistan

Etiology and Audiological Outcomes at 3 Years for 364 Children in Australia

The contribution of GJB2 mutations to slight or mild hearing loss in Australian elementary school children

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