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

Regie Lyn P Santos; Hatem El-Shanti; Shaheen Sikandar; Kwanghyuk Lee; Attya Bhatti; Kai Yan; Maria H Chahrour; Nathan McArthur; Thanh L Pham; Amjad Abdullah Mahasneh; Wasim Ahmad; Suzanne M Leal

doi:10.1007/s00109-005-0015-3

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

Journal article

Peer reviewed

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

Regie Lyn P Santos, Hatem El-Shanti, Shaheen Sikandar, Kwanghyuk Lee, Attya Bhatti, Kai Yan, Maria H Chahrour, Nathan McArthur, Thanh L Pham, Amjad Abdullah Mahasneh, …

Journal of molecular medicine (Berlin, Germany), Vol.84(3), pp.226-231

03/2006

DOI: 10.1007/s00109-005-0015-3

PMCID: PMC2909111

PMID: 16389551

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Abstract

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.

Autosomal recessive nonsyndromic hearing impairment

TMIE

Pakistan

Prevalence

Jordan

Details

Title: Subtitle: Novel sequence variants in the TMIE gene in families with autosomal recessive nonsyndromic hearing impairment
Creators: Regie Lyn P Santos - Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Alkek N1619.01, Houston, TX 77030, USA. Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics, Erasmus Medical Centre, Rotterdam, The Netherlands
Hatem El-Shanti - Department of Pediatrics, Division of Medical Genetics, University of Iowa Hospital and Clinics, Iowa City, IA, USA. Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid, Jordan
Shaheen Sikandar - Department of Biological Sciences, Quaid-I-Azam University, Islamabad, Pakistan
Kwanghyuk Lee - Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Alkek N1619.01, Houston, TX 77030, USA
Attya Bhatti - Department of Biological Sciences, Quaid-I-Azam University, Islamabad, Pakistan
Kai Yan - Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Alkek N1619.01, Houston, TX 77030, USA
Maria H Chahrour - Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Alkek N1619.01, Houston, TX 77030, USA
Nathan McArthur - Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Alkek N1619.01, Houston, TX 77030, USA
Thanh L Pham - Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Alkek N1619.01, Houston, TX 77030, USA
Amjad Abdullah Mahasneh - Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid, Jordan
Wasim Ahmad - Department of Biological Sciences, Quaid-I-Azam University, Islamabad, Pakistan
Suzanne M Leal - Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Alkek N1619.01, Houston, TX 77030, USA, Tel.: +1-713-7984011, Fax: +1-713-7984373
Resource Type: Journal article
Publication Details: Journal of molecular medicine (Berlin, Germany), Vol.84(3), pp.226-231
DOI: 10.1007/s00109-005-0015-3
PMID: 16389551
PMCID: PMC2909111
NLM abbreviation: J Mol Med (Berl)
ISSN: 0946-2716
eISSN: 1432-1440
Publisher: Springer Science and Business Media LLC
Language: English
Date published: 03/2006
Academic Unit: Stead Family Department of Pediatrics; Medical Genetics and Genomics
Record Identifier: 9984093209402771

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