A novel autosomal recessive non-syndromic deafness locus (DFNB35) maps to 14q24.1–14q24.3 in large consanguineous kindred from Pakistan

Ansar, Muhammad; Din, Mohammad Amin ud; Arshad, Muhammad Imran; Sohail, Muhammad; Faiyaz-Ul-Haque, Mohammad; Haque, Sayedul; Ahmad, Wasim; Leal, Suzanne M.

doi:10.1038/sj.ejhg.5200905

Cited by 22 publications

(14 citation statements)

References 8 publications

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“…it is the most common cause of nonsyndromic HL and was the first identified gene is GJB2; it is encoded as connexin 26 (DFNA3a/DFNB1a) [ 54 ]. Other connexins related to nonsyndromic HL are connexin 30 ( GJB6 , DFNA3b/DFNB1b) [ 55 , 56 ] and connexin 31 ( GJB3 , DFNA2b/DFNB91) [ 57 , 58 ].…”

Section: Genes and Proteins Related To Nonsyndromic Hearing Lossmentioning

confidence: 99%

Genetics of Nonsyndromic Congenital Hearing Loss

Eğilmez

Kalcıoğlu

2016

Scientifica

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Congenital hearing impairment affects nearly 1 in every 1000 live births and is the most frequent birth defect in developed societies. Hereditary types of hearing loss account for more than 50% of all congenital sensorineural hearing loss cases and are caused by genetic mutations. HL can be either nonsyndromic, which is restricted to the inner ear, or syndromic, a part of multiple anomalies affecting the body. Nonsyndromic HL can be categorised by mode of inheritance, such as autosomal dominant (called DFNA), autosomal recessive (DFNB), mitochondrial, and X-linked (DFN). To date, 125 deafness loci have been reported in the literature: 58 DFNA loci, 63 DFNB loci, and 4 X-linked loci. Mutations in genes that control the adhesion of hair cells, intracellular transport, neurotransmitter release, ionic hemeostasis, and cytoskeleton of hair cells can lead to malfunctions of the cochlea and inner ear. In recent years, with the increase in studies about genes involved in congenital hearing loss, genetic counselling and treatment options have emerged and increased in availability. This paper presents an overview of the currently known genes associated with nonsyndromic congenital hearing loss and mutations in the inner ear.

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Section: Genes and Proteins Related To Nonsyndromic Hearing Lossmentioning

confidence: 99%

Genetics of Nonsyndromic Congenital Hearing Loss

Eğilmez

Kalcıoğlu

2016

Scientifica

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“…The ESRRB gene was mapped to 14q24.3 by fluorescence in situ hybridization. Five different homozygous mutations have so far been reported (47,48). …”

Section: Genes Implicated In Cochlear Homeostasismentioning

confidence: 99%

Autosomal recessive nonsyndromic deafness genes: a review

Duman¹

2012

Front Biosci

131

104

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More than 50 percent of prelingual hearing loss is genetic in origin, and of these up to 93 percent are monogenic autosomal recessive traits. Some forms of genetic deafness can be recognized by their associated syndromic features, but in most cases, hearing loss is the only finding and is referred to as nonsyndromic deafness. To date, more than 700 different mutations have been identified in one of 42 genes in individuals with autosomal recessive nonsyndromic hearing loss (ARNSHL). Reported mutations in GJB2, encoding connexin 26, makes this gene the most common cause of hearing loss in many populations. Other relatively common deafness genes include SLC26A4, MYO15A, OTOF, TMC1, CDH23, and TMPRSS3. In this report we summarize genes and mutations reported in families with ARNSHL. Founder effects were demonstrated for some recurrent mutations but the most significant findings are the extreme locus and allelic heterogeneity and different spectrum of genes and mutations in each population.

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“…The critical region had an overlap of 1.1 cM with DFNB35 (MIM %608565). 8 One of the genes in this overlapping region was the estrogen-related receptor beta gene ESRRB (MIM #602167) that is a member of the estrogen-receptor family. Sequence analysis of this gene in the affected individuals of family TR-21, in the original DFNB35 family, and in three additional DFNB35-linked families from Pakistan indicate that mutations of ESRRB are causative for early-onset hearing impairment.…”

Section: Introductionmentioning

confidence: 99%

Mutations of ESRRB Encoding Estrogen-Related Receptor Beta Cause Autosomal-Recessive Nonsyndromic Hearing Impairment DFNB35

Collin

Kalay

Tariq

et al. 2008

The American Journal of Human Genetics

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100

102

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In a large consanguineous family of Turkish origin, genome-wide homozygosity mapping revealed a locus for recessive nonsyndromic hearing impairment on chromosome 14q24.3-q34.12. Fine mapping with microsatellite markers defined the critical linkage interval to a 18.7 cM region flanked by markers D14S53 and D14S1015. This region partially overlapped with the DFNB35 locus. Mutation analysis of ESRRB, a candidate gene in the overlapping region, revealed a homozygous 7 bp duplication in exon 8 in all affected individuals. This duplication results in a frame shift and premature stop codon. Sequence analysis of the ESRRB gene in the affected individuals of the original DFNB35 family and in three other DFNB35-linked consanguineous families from Pakistan revealed four missense mutations. ESRRB encodes the estrogen-related receptor beta protein, and one of the substitutions (p.A110V) is located in the DNA-binding domain of ESRRB, whereas the other three are substitutions (p.L320P, p.V342L, and p.L347P) located within the ligand-binding domain. Molecular modeling of this nuclear receptor showed that the missense mutations are likely to affect the structure and stability of these domains. RNA in situ hybridization in mice revealed that Esrrb is expressed during inner-ear development, whereas immunohistochemical analysis showed that ESRRB is present postnatally in the cochlea. Our data indicate that ESRRB is essential for inner-ear development and function. To our knowledge, this is the first report of pathogenic mutations of an estrogen-related receptor gene.

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A novel autosomal recessive non-syndromic deafness locus (DFNB35) maps to 14q24.1–14q24.3 in large consanguineous kindred from Pakistan

Cited by 22 publications

References 8 publications

Genetics of Nonsyndromic Congenital Hearing Loss

Genetics of Nonsyndromic Congenital Hearing Loss

Autosomal recessive nonsyndromic deafness genes: a review

Mutations of ESRRB Encoding Estrogen-Related Receptor Beta Cause Autosomal-Recessive Nonsyndromic Hearing Impairment DFNB35

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