Novel sequence variants in theTMC1 gene in Pakistani families with autosomal recessive hearing impairment

Santos, Regie Lyn P.; Wajid, Muhammad; Khan, Mohammad Nasim Imtiaz; McArthur, Nathan; Pham, Tam Dan N.; Bhatti, Attya; Lee, Kwanghyuk; Irshad, Saba; Mir, Asif; Yan, Kai; Chahrour, Maria H.; Ansar, Muhammad; Ahmad, Wasim; Leal, Suzanne M.

doi:10.1002/humu.9374

Cited by 51 publications

(59 citation statements)

References 23 publications

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“…Other variants were also detected, including IVS5 + 1G > T, p.P514L, and p.C515R. Santos et al (2005) reported a prevalence of 4.4% of NSHL due to TMC1 in the Pakistani population. We previously estimated that TMC1 mutations account for approximately 5% of recessive deafness in a mixed cohort of 230 Pakistani and Indian families (6/10 Punjabi families) (Kurima et al, 2002).…”

Section: Dfnb7/11/tmc1mentioning

confidence: 92%

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The Genetic Basis of Nonsyndromic Hearing Loss in Indian and Pakistani Populations

Yan

Kannan-Sundhari

Vishwanath

et al. 2015

Genetic Testing and Molecular Biomarkers

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Section: Dfnb7/11/tmc1mentioning

confidence: 92%

“…Screening of 430 affected subjects from 196 families for GJB2 variations by Santos et al (2005) showed that only 6.1% of the families had GJB2-related HL. W24X and W77X were found to be the most common.…”

Section: Dfnb1/gjb2mentioning

confidence: 99%

The Genetic Basis of Nonsyndromic Hearing Loss in Indian and Pakistani Populations

Yan

Kannan-Sundhari

Vishwanath

et al. 2015

Genetic Testing and Molecular Biomarkers

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“…In this population of Pakistani families with ARNSHI, the prevalence of putatively functional variants in the GJB2 gene is 6.1% (95% CI 3.2-10.4) [15], while the prevalence of putatively functional TMC1 (MIM no. 606706) variants is 4.4% (95% CI 1.9-8.6) [16]. The importance of the TMIE gene as a cause of HI cannot be known until other populations are studied.…”

Section: Discussionmentioning

confidence: 99%

Novel sequence variants in the TMIE gene in families with autosomal recessive nonsyndromic hearing impairment

et al. 2005

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To date, 37 genes have been identified for nonsyndromic hearing impairment (NSHI). Identifying the functional sequence variants within these genes and knowing their population-specific frequencies is of public health value, in particular for genetic screening for NSHI. To determine putatively functional sequence variants in the transmembrane inner ear (TMIE) gene in Pakistani and Jordanian families with autosomal recessive (AR) NSHI, four Jordanian and 168 Pakistani families with ARNSHI that is not due to GJB2 (CX26) were submitted to a genome scan. Twopoint and multipoint parametric linkage analyses were performed, and families with logarithmic odds (LOD) scores of 1.0 or greater within the TMIE region underwent further DNA sequencing. The evolutionary conservation and location in predicted protein domains of amino acid residues where sequence variants occurred were studied to elucidate the possible effects of these sequence variants on function. Of seven families that were screened for TMIE, putatively functional sequence variants were found to segregate with hearing impairment in four families but were not seen in not less than 110 ethnically matched control chromosomes. The previously reported c. 241C>T (p.R81C) variant was observed in two Pakistani families. Two novel variants, c.92A>G (p.E31G) and the splice site mutation c.212-2A>C, were identified in one Pakistani and one Jordanian family, respectively. The c.92A>G (p.E31G) variant occurred at a residue that is conserved in the mouse and is predicted to be extracellular. Conservation and potential functionality of previously published mutations were also examined. The prevalence of functional TMIE variants in Pakistani families is 1.7% [95% confidence interval (CI) 0.3-4.8]. Further studies on the spectrum, prevalence rates, and functional effect of sequence variants in the TMIE gene in other populations should demonstrate the true importance of this gene as a cause of hearing impairment.

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“…Mutations in TMC1 are a common cause of ARNSHL in India, Pakistan, Tunisia, and Turkey where they account for the hearing-loss phenotype in 3-6% of families (Kurima et al, 2002;Kalay et al, 2005;Santos et al, 2005;Kitajiri et al, 2007;Hilgert et al, 2008;Tlili et al, 2008;Sirmaci et al, 2009). Of the 29 reported mutations in this gene, the p.R34X mutation is the most frequent and accounts for over 30% of all TMC1 ARNSHL-causing mutations.…”

Section: Discussionmentioning

confidence: 99%

“…Twenty-nine different mutations of the transmembrane channel-like gene 1 (TMC1) gene (GenBank accession number: NM_138691.2) have been reported in 48 families with ARNSHL (Kurima et al, 2002;Kalay et al, 2005;Meyer et al, 2005;Santos et al, 2005;Kitajiri et al, 2007;Hilgert et al, 2008;Tlili et al, 2008;Sirmaci et al, 2009). The most common recessive mutation for hearing loss in the TMC1 gene is p.R34X.…”

Section: Introductionmentioning

confidence: 99%

High Frequency of the p.R34X Mutation in the TMC1 Gene Associated with Nonsyndromic Hearing Loss Is Due to Founder Effects

Said

Hmani-Aifa

Amar

et al. 2010

Genetic Testing and Molecular Biomarkers

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Novel sequence variants in theTMC1 gene in Pakistani families with autosomal recessive hearing impairment

Cited by 51 publications

References 23 publications

The Genetic Basis of Nonsyndromic Hearing Loss in Indian and Pakistani Populations

The Genetic Basis of Nonsyndromic Hearing Loss in Indian and Pakistani Populations

Novel sequence variants in the TMIE gene in families with autosomal recessive nonsyndromic hearing impairment

High Frequency of the p.R34X Mutation in the TMC1 Gene Associated with Nonsyndromic Hearing Loss Is Due to Founder Effects

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