Screening of families with autosomal recessive non‐syndromic hearing impairment (ARNSHI) for mutations in GJB2 gene: Indian scenario

Maheshwari, Manjula; Vijaya, R.; Ghosh, Manju; Shastri, Shivaram; Kabra, Madhulika; Menon, Purnima

doi:10.1002/ajmg.a.20014

Cited by 59 publications

(64 citation statements)

References 19 publications

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“…W24X is another commonly found allele, and has been associated with arnSHi in the north and south of india (36,37). The incorporation of a stop codon in this mutation at codon 24 of cx26 causes the formation of a protein that is just 1/10 the length of the wild-type protein (32).…”

Section: Discussionmentioning

confidence: 99%

Mutations of the Connexin 26 gene in families with non-syndromic hearing loss

et al. 2011

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Abstract. autosomal recessive non-syndromic hearing impairment (arnSHi) is caused by mutations in the gap junction gene GJB2 (connexin 26; cx26) in numerous human populations. The aim of this study was to determine the frequency of six GJB2 mutations in 50 Syrian families with congenital deafness and in 180 controls. Pcr-rFlP was used to detect the 35delG, 167delT, M34T, W24X, W77r and e47X mutations, and direct sequencing was performed for the 35delG mutation. The data revealed a high prevalence of the 35delG mutation among deaf families. Homozygous 35delG was detected in fifteen of the Syrian families (30%). a compound heterozygous genotype was observed in two families: one with the 35delG/167delT mutation (2%) and one with the 35delG/M34T mutation (2%). Nine families were heterozygous with no second identified mutation in Cx26: four with 35delG+/unknown (8%), four with 167delT/unknown (8%) and one with M34T/unknown (2%). The W24X, W77R and e47X mutations were not detected in any of the study subjects. Three individuals with the heterozygous 35delG genotype (1.66%) and five with the heterozygous 167delT genotype (2.77%) were detected among the controls. No other mutations were found among the controls. These results have important implications for the diagnosis and counseling of families with cx26 deafness.

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Section: Discussionmentioning

confidence: 99%

Mutations of the Connexin 26 gene in families with non-syndromic hearing loss

et al. 2011

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“…In approaching the general hearing-impaired population, there are basically three kinds of patient sources: hospitals, rehabilitation facilities and deafness schools. Some studies recruited patients through hospitals [Belintani Piatto et al, 2004;Dalamon et al, 2005], others from the deafness boarding schools or rehabilitation facilities [Kalay et al, 2005], while others recruited subjects from a mix of both [Gurtler et al, 2003;Hwa et al, 2003;Maheshwari et al, 2003]. Theoretically, there are advantages and disadvantages for each type of patient source.…”

Section: Discussionmentioning

confidence: 99%

“…The most famous gene with the aforementioned characteristics is a gap junction protein-encoding gene, the GJB2 (or Cx26 ) gene (MIM * 121011). Its mutations have been documented with high prevalence in hearing-impaired populations of different ethnic backgrounds, including Caucasians [Denoyelle et al, 1997;Frei et al, 2002;Gabriel et al, 2001;Gurtler et al, 2003;Pandya et al, 2003], East Asians Hwa et al, 2003;Liu et al, 2002;Park et al, 2000], South Americans [Belintani Piatto et al, 2004;Dalamon et al, 2005], Indians [Maheshwari et al, 2003], Jews [Morell et al, 1998], Moroccans [Gazzaz et al, 2005], Turks [Kalay et al, 2005] and Gypsies [Alvarez et al, 2005]. Two other common deafness genes with high prevalence and worldwide distribution are the SLC26A4 (PDS) gene (MIM * 605646) and the mitochondrial 12S rRNA (MTRNR1) gene (MIM * 561000).…”

Section: Introductionmentioning

confidence: 99%

Prospective Mutation Screening of Three Common Deafness Genes in a Large Taiwanese Cohort with Idiopathic Bilateral Sensorineural Hearing Impairment Reveals a Difference in the Results between Families from Hospitals and Those from Rehabilitation Facilities

Chen²,

Chiu³

et al. 2007

Audiol Neurotol

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Accurate epidemiological data on common deafness genes are essential to improve the efficiency and to reduce the cost of molecular diagnosis. They may depend on several factors, including a clear delineation of the source of patients being studied. In the present study, we hypothesize that patients with idiopathic sensorineural hearing loss recruited from different sources might reveal discrepancies in the epidemiological results of genetic screening, because patients from different sources might demonstrate distinct clinical or audiologic features and thus result in biased selection of subjects. To elucidate the relative importance of common deafness genes in Taiwanese and to verify our hypothesis, we conducted a prospective project screening mutations in GJB2, SLC26A4 and mitochondrial 12S rRNA gene in a total of 420 Taiwanese families with idiopathic bilateral sensorineural hearing loss, of which 325 families were recruited from hospitals and 95 from hearing rehabilitation facilities. Allele frequencies of common mutations in these three genes and distributions of the corresponding genotypes were then compared between the two groups. The allele frequencies of mutations in SLC26A4, GJB2 and mitochondrial 12S rRNA in the probands of the 420 families were 14.4, 21.7 and 3.8%, respectively. The allele frequency of SLC26A4 mutations in the hospital group was significantly higher than that in the rehabilitation facility group (16.2 vs. 8.4%, χ²-test, p < 0.05), whereas no difference in the frequencies of GJB2 mutations and mitochondrial 12S rRNA mutations was found between the two groups. Distributions of probands classified by SLC26A4 genotypes were also different between the two groups (χ²-test, p < 0.05). Accordingly, a discrepancy in the genetic screening results might exist between different sources of idiopathic hearing-impaired patients. Further analysis of audiological results and construction of a logistic regression model showed that different audiological features, namely hearing levels and hearing loss patterns, might be responsible for the unequal distributions of mutations and probands between the hospital and rehabilitation facility groups.

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“…13 -15 The threedimensional structure of M34A, a human Cx26 mutation, reveals a prominent electron density in the pore of each hemichannel, suggesting that physical blocking may be important in gap junction channel regulation. 16 Although W24X is known to be a common Cx26 mutation in India, 17,18 the full spectrum of mutations of this gene occurring in India is not known. We present here the results of a study of Cx26 in 530 individuals exhibiting non-syndromic, sensorineural hearing loss, in which we identified four novel Cx26 mutations and 14 mutations that have been described earlier.…”

Section: Introductionmentioning

confidence: 99%

Functional consequences of novel connexin 26 mutations associated with hereditary hearing loss

et al. 2008

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In a study of 530 individuals with non-syndromic, sensorineural hearing loss, we identified 18 mutations at connexin 26 (Cx26), four of which are novel (À23G4T, I33T, 377_383dupTCCGCAT, W172R) and the remaining 14 (ivs1 þ 1G4A, M1V, 35delG, W24X, I35S, V37I, R75W, W77X, 312del14, E120del, Q124X, Y136X, R143W, R184P) being mutations previously described. To gain insight into functional consequences of these mutations, cellular localization of the mutant proteins and their ability to permit lucifer yellow transfer between cells was studied in seven of them (W24X, I33T, I35S, R75W, E120del, W172R and R184P). I35S and R184P showed impaired trafficking of the protein to the plasma membrane. I33T, R75W, E120del and W172R showed predominantly membrane localization but did not form functional gap junction channels. Surprisingly, W24X, a protein-truncating mutation, apparently permits formation of a full-length protein, perhaps due to a stop codon read-through mechanism. These results provide further evidence that Cx26 mutations affect gap junction activity by mis-regulation at multiple levels.

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Screening of families with autosomal recessive non‐syndromic hearing impairment (ARNSHI) for mutations in GJB2 gene: Indian scenario

Cited by 59 publications

References 19 publications

Mutations of the Connexin 26 gene in families with non-syndromic hearing loss

Mutations of the Connexin 26 gene in families with non-syndromic hearing loss

Prospective Mutation Screening of Three Common Deafness Genes in a Large Taiwanese Cohort with Idiopathic Bilateral Sensorineural Hearing Impairment Reveals a Difference in the Results between Families from Hospitals and Those from Rehabilitation Facilities

Functional consequences of novel connexin 26 mutations associated with hereditary hearing loss

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