Ethnicity and mutations in GJB2 (connexin 26) and GJB6 (connexin 30) in a multi-cultural Canadian paediatric Cochlear Implant Program

Propst, Evan J.; Stockley, Tracy L.; Gordon, Karen A.; Harrison, Robert V.; Papsin, Blake C.

doi:10.1016/j.ijporl.2005.07.013

Cited by 32 publications

(36 citation statements)

References 55 publications

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“…The GJB2 gene has been found to account for approximately 50% of people with autosomal recessive nonsyndromic hearing loss in various ethnic populations [Morton, 1991;Marazita et al, 1993;Zelante et al, 1997;Kelley et al, 1998;Cohn et al, 1999;Kudo et al, 2001;Kupka et al, 2002;Snoeckx et al, 2005;del Castillo et al, 2005;Propst et al, 2006]. Identification of a GJB2 mutation enables parents to know the cause of a newborn's hearing loss soon after birth.…”

Section: Introductionmentioning

confidence: 99%

Assessing parental attitudes toward genetic testing for childhood hearing loss: Before and after genetic consultation

Steinberg

Bain

et al. 2007

American J of Med Genetics Pt A

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We report on the development of a Genetic Attitude Assessment Tool (GAAT) to measure parental attitudes in contemplating genetic testing for childhood hearing loss, and to examine the differences in assessments made before and after genetic counseling. The GAAT tool was administered to a convenient sample of 119 parents of children with bilateral sensorineural hearing loss. The respondents completed the survey either before (n = 77) or after (n = 42) genetic counseling. Exploratory Factor Analysis was applied to identify and quantify the underlying psychosocial structure. Our results showed the validated 54-item GAAT instrument contains six subscales: (1) "test intention," (2) "beliefs in non-genetic causes of hearing loss," (3) "deferral of decision to undergo genetic testing," (4) "appropriate use of genetic testing results," (5) "beliefs in the benefits," and (6) "concerns about stigma." The respondents who answered the survey after genetic counseling had higher "test intention" (P = 0.017) and endorsed to a greater extent "beliefs in the benefits" (P < 0.001). They believed to a lesser extent that childhood hearing loss was due to "non-genetic causes" (P < 0.001) and were less inclined to prefer "decision deferral" (P = 0.031). Respondents who themselves had a hearing loss expressed a significantly weaker belief in "non-genetic causes" of hearing loss (P < 0.0001). In conclusion the validated GAAT instrument is responsive to changes in parental attitudes after genetic counseling. The GAAT may be used to monitor parental attitudes serially, to further understand how parental attitudes change from pre genetic counseling, post genetic counseling, to post test result disclosure.

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Section: Introductionmentioning

confidence: 99%

Assessing parental attitudes toward genetic testing for childhood hearing loss: Before and after genetic consultation

Steinberg

Bain

et al. 2007

American J of Med Genetics Pt A

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“…The results we obtained undoubtedly show that mutations in the connexin 26 gene are a main reason for severe to profound congenital deafness in the Bulgarian population with 55% carriers of a DNA sequence different from the WT. Taking account of homozygous (N = 20) and heterozygous patients (N = 5), the c.35delG mutation was the most frequently detected, and being responsible for 86% of the changes in the GJB2 gene which corresponds to similar studies of other Caucasian populations [4,8,9]. This mutation is estimated to be about 500 generations or 10,000 years old [13].…”

Section: Discussionmentioning

confidence: 75%

“…Despite the fact that the patient presented with profound hearing loss, the clinical significance of this new mutation remains to be determined. The other existing mutation L90P was first described in two non-related patients from Italy and later on in such from Austria, Hungary and Slovakia [8]. It is a result of the substitution of T with C in 269th position, which leads to the exchange of leucine to proline at position 90.…”

Section: Discussionmentioning

confidence: 99%

“…According to a number of studies, along with c.35delG, W24X is one of the most common mutations of the GJB2 gene in Central and South-eastern Europe [4], but a larger study group is necessary to compare adequately precise frequencies of occurrence in our population. The mutation was first described in two Pakistani families and consequently in Hungarians, East Indians, Iranians, Slovak Roma and Turkish descendants [8].…”

Section: Discussionmentioning

confidence: 99%

“…Connexin 26 is part of a large family of gap junction proteins involved in direct cell-to-cell transfer of small molecules and ions, and is considered to be vital for the recycling of endolyphatic potassium ions as it is distributed widely in the cochlea, stria vascularis, basilar membrane, limbus, and spiral prominence [5][6][7]. Mutations in GJB2 are found to be responsible for 40-60% of genetic sensorineural childhood deafness, since it is presumed that they lead >to altered potassium recirculation and accumulation of potassium in the cochlear endolymph which finally results in hair cell destruction and deafness [8].…”

Section: Introductionmentioning

confidence: 99%

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Prevalence of GBJ2 mutations in patients with severe to profound congenital nonsyndromic sensorineural hearing loss in Bulgarian population

Попова

Kaneva

Varbanova

et al. 2011

Eur Arch Otorhinolaryngol

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Objective of the study is to assess the prevalence of Connexin 26 (GJB2) mutation in patients with congenital nonsyndromic sensorineural hearing loss in Bulgarian population. Study design is done prospectively. Patient inclusion criteria for this study were diagnosis of congenital nonsyndromic hearing loss, and absence of potential sibling relationships between patients included in the study (anamnestic pedigree for at least three generations). Patients were excluded from the study group if one of the following conditions were present: secondary hearing loss (cytomegalovirus, rubella, meningo-encephalitis, mastoiditis, other infections, posterior fossa tumors, etc.), exposure to drugs or other prenatal or perinatal etiology of deafness, and congenital syndromic hearing loss. Genomic DNA samples from whole blood were tested with sequence analysis for mutations in the coding region of the GJB2. Results state that 51 patients were analyzed for GJB2 mutations. Twenty of the patients (39%) with mutant alleles were homozygous for the c.35delG mutation (c.35delG/c.35delG) and four patients (8%) presented as heterozygotes (c.35delG/WT). In one patient, who carried a heterozygous mutation c.35delG, a second mutation was found-312del114. Additionally, in two other patients were discovered the mutations Trp24X (W24X) and, respectively, Arg127His(R127H), both in heterozygous states. From the whole study group there was only one patient with compound heterozygous genotype-p.Leu90Pro(L90P)/p.Ile121Asn. The latter one has never been reported in the literature so far. In conclusion, this study determines the importance of connexin 26 mutations in Bulgarian children with severe to profound congenital nonsyndromic sensorineural hearing loss, the prevalence of the different mutation variants and their relationship with the ethnical background of the patients. In addition, we report for the first time a novel mutation in the GJB2 gene.

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Homozygosity for the V37I GJB2 mutation in fifteen probands with mild to moderate sensorineural hearing impairment: Further confirmation of pathogenicity and haplotype analysis in Asian populations

Gallant

Francey

Tsai

et al. 2013

American J of Med Genetics Pt A

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Hearing impairment affects 1 in 650 newborns, making it the most common congenital sensory impairment. Autosomal recessive nonsyndromic sensorineural hearing impairment (ARNSHI) comprises 80% of familial hearing impairment cases. Mutations in GJB2 account for a significant number of ARNSHI (and up to 50% of documented recessive (e.g. more than 1 affected sibling) hearing impairment in some populations). Mutations in the GJB2 gene are amongst the most common causes of hearing impairment in populations of various ethnic backgrounds. Two mutations of this gene, 35delG and 167delT, account for the majority of reported mutations in Caucasian populations, especially those of Mediterranean and Ashkenazi Jewish background. The 235delC mutation is most prevalent in East Asian populations. Some mutations are of less well characterized significance. The V37I missense mutation, common in Asian populations, was initially described as a polymorphism and later as a potentially pathogenic mutation. We report here on 15 unrelated individuals with ARNSHI and homozygosity for the V37I GJB2 missense mutation. Nine individuals are of Chinese ancestry, two are of unspecified Asian descent, one is of Japanese descent, one individual is of Vietnamese ancestry, one of Philippine background and one of Italian and Cuban/Caucasian background. Homozygosity for the V37I GJB2 mutation may be a more common pathogenic missense mutation in Asian populations, resulting in mild to moderate sensorineural hearing impairment. We report a presumed haplotype block specific to East Asian individuals with the V37I mutation encompassing the GJB2 gene that may account for the high prevalence in East Asian populations.

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Ethnicity and mutations in GJB2 (connexin 26) and GJB6 (connexin 30) in a multi-cultural Canadian paediatric Cochlear Implant Program

Cited by 32 publications

References 55 publications

Assessing parental attitudes toward genetic testing for childhood hearing loss: Before and after genetic consultation

Assessing parental attitudes toward genetic testing for childhood hearing loss: Before and after genetic consultation

Prevalence of GBJ2 mutations in patients with severe to profound congenital nonsyndromic sensorineural hearing loss in Bulgarian population

Homozygosity for the V37I GJB2 mutation in fifteen probands with mild to moderate sensorineural hearing impairment: Further confirmation of pathogenicity and haplotype analysis in Asian populations

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