Dataset Information

Autosomal Recessive Nonsyndromic Hearing Impairment due to a Novel Deletion in the RDX Gene.

ABSTRACT: The RDX gene anchors cytoskeletal actin of stereocilia to hair cell transmembrane and is responsible for autosomal recessive nonsyndromic hearing impairment (ARNSHI) due to DFNB24. A genome scan was performed using DNA samples from a consanguineous Pakistani family with ARNSHI. A significant maximum two-point LOD score of 4.5 (? = 0) and multipoint LOD score of 5.8 were achieved at marker D11S1998 (chr11?:?117.20?Mb). The region of homozygosity is bounded by markers D11S2000 (105.06?Mb) and D11S4464 (123.13?Mb) and contains the NSHI genes TECTA and RDX. Although no potentially causal variants were identified in the TECTA gene, within the RDX gene a novel deletion c.1076_1079delTTAA (p.Ile359Lysfs?6) was identified. The RDX deletion segregates with ARNSHI within the family and was not observed in 500 control chromosomes. It is predicted to cause premature truncation of radixin at the ?-helical domain and to result in nonfunctional transcripts within the cochlea. RDX isoforms which encode the coiled-coil region of the ?-helical domain are deemed necessary for proper function of hair cell stereocilia.

SUBMITTER: Lee K

PROVIDER: S-EPMC3335613 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Publications

Autosomal Recessive Nonsyndromic Hearing Impairment due to a Novel Deletion in the RDX Gene.

Lee Kwanghyuk K Amin Ud Din Mohammad M Ansar Muhammad M Santos-Cortez Regie Lyn P RL Ahmad Wasim W Leal Suzanne M SM

Genetics research international 20111101

The RDX gene anchors cytoskeletal actin of stereocilia to hair cell transmembrane and is responsible for autosomal recessive nonsyndromic hearing impairment (ARNSHI) due to DFNB24. A genome scan was performed using DNA samples from a consanguineous Pakistani family with ARNSHI. A significant maximum two-point LOD score of 4.5 (θ = 0) and multipoint LOD score of 5.8 were achieved at marker D11S1998 (chr11 : 117.20 Mb). The region of homozygosity is bounded by markers D11S2000 (105.06 Mb) and D11S ...[more]

PMID: 22567349

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Project description: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. Two-point 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.

Dataset Information

Autosomal Recessive Nonsyndromic Hearing Impairment due to a Novel Deletion in the RDX Gene.

Publications

Autosomal Recessive Nonsyndromic Hearing Impairment due to a Novel Deletion in the RDX Gene.

Similar Datasets

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