Journal article
Loss-of-Function Mutations of ILDR1 Cause Autosomal-Recessive Hearing Impairment DFNB42
American journal of human genetics, Vol.88(2), pp.127-137
2011
DOI: 10.1016/j.ajhg.2010.12.011
PMCID: PMC3035704
PMID: 21255762
Abstract
By using homozygosity mapping in a consanguineous Pakistani family, we detected linkage of nonsyndromic hearing loss to a 7.6 Mb region on chromosome 3q13.31-q21.1 within the previously reported
DFNB42 locus. Subsequent candidate gene sequencing identified a homozygous nonsense mutation (c.1135G>T [p.Glu379X]) in
ILDR1 as the cause of hearing impairment. By analyzing additional consanguineous families with homozygosity at this locus, we detected
ILDR1 mutations in the affected individuals of 10 more families from Pakistan and Iran. The identified
ILDR1 variants include missense, nonsense, frameshift, and splice-site mutations as well as a start codon mutation in the family that originally defined the
DFNB42 locus.
ILDR1 encodes the evolutionarily conserved immunoglobulin-like domain containing receptor 1, a putative transmembrane receptor of unknown function. In situ hybridization detected expression of
Ildr1, the murine ortholog, early in development in the vestibule and in hair cells and supporting cells of the cochlea. Expression in hair cell- and supporting cell-containing neurosensory organs is conserved in the zebrafish, in which the
ildr1 ortholog is prominently expressed in the developing ear and neuromasts of the lateral line. These data identify loss-of-function mutations of
ILDR1, a gene with a conserved expression pattern pointing to a conserved function in hearing in vertebrates, as underlying nonsyndromic prelingual sensorineural hearing impairment.
Details
- Title: Subtitle
- Loss-of-Function Mutations of ILDR1 Cause Autosomal-Recessive Hearing Impairment DFNB42
- Creators
- Guntram Borck - Institute of Human Genetics, University of Cologne, 50931 Cologne, GermanyAtteeq Ur Rehman - Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USAKwanghyuk Lee - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USAHans-Martin Pogoda - Institute for Developmental Biology, University of Cologne, 50674 Cologne, GermanyNaseebullah Kakar - Department of Biotechnology and Informatics, BUITEMS, Quetta 78300, PakistanSimon von Ameln - Institute of Human Genetics, University of Cologne, 50931 Cologne, GermanyNicolas Grillet - Dorris Neuroscience Center and Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USAMichael S Hildebrand - Department of Otolaryngology, Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USAZubair M Ahmed - Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Research Foundation, and the Department of Ophthalmology, College of Medicine, University of Cincinnati, OH 45229, USAGudrun Nürnberg - Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, GermanyMuhammad Ansar - Department of Biochemistry, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad 45320, PakistanSulman Basit - Department of Biochemistry, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad 45320, PakistanQamar Javed - Department of Biochemistry, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad 45320, PakistanRobert J Morell - Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USANabilah Nasreen - Department of Biotechnology and Informatics, BUITEMS, Quetta 78300, PakistanA. Eliot Shearer - Department of Otolaryngology, Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USAAdeel Ahmad - King Edward Medical University, Mayo Hospital, Lahore 54000, PakistanKimia Kahrizi - Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran 19834, IranRehan S Shaikh - National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore 54500, PakistanRana A Ali - National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore 54500, PakistanShaheen N Khan - National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore 54500, PakistanIngrid Goebel - Institute of Human Genetics, University of Cologne, 50931 Cologne, GermanyNicole C Meyer - Department of Otolaryngology, Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USAWilliam J Kimberling - Department of Genetics, Boys Town National Research Hospital, Omaha, NE 68131, USAJennifer A Webster - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USADietrich A Stephan - Institute for Individualized Health (IGNITE), Palo Alto, CA 94301, USAMartin R Schiller - School of Life Sciences, University of Nevada Las Vegas, Las Vegas, NV 89052, USAMelanie Bahlo - Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, AustraliaHossein Najmabadi - Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran 19834, IranPeter G Gillespie - Oregon Hearing Research Center and Vollum Institute, Oregon Health & Science University, Portland, OR 97239, USAPeter Nürnberg - Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, GermanyBernd Wollnik - Institute of Human Genetics, University of Cologne, 50931 Cologne, GermanySaima Riazuddin - Laboratory of Molecular Genetics, Division of Pediatric Otolaryngology, Head and Neck Surgery, Cincinnati Children's Hospital Research Foundation, and the Department of Otolaryngology, College of Medicine, University of Cincinnati, OH, 45229 USARichard J.H Smith - Department of Otolaryngology, Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USAWasim Ahmad - Department of Biochemistry, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad 45320, PakistanUlrich Müller - Dorris Neuroscience Center and Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USAMatthias Hammerschmidt - Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, GermanyThomas B Friedman - Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USASheikh Riazuddin - Allama Iqbal Medical College/Jinnah Hospital Complex, University of Health Sciences, Lahore 54550, PakistanSuzanne M Leal - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USAJamil Ahmad - Department of Biotechnology and Informatics, BUITEMS, Quetta 78300, PakistanChristian Kubisch - Institute of Human Genetics, University of Cologne, 50931 Cologne, Germany
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.88(2), pp.127-137
- DOI
- 10.1016/j.ajhg.2010.12.011
- PMID
- 21255762
- PMCID
- PMC3035704
- NLM abbreviation
- Am J Hum Genet
- ISSN
- 0002-9297
- eISSN
- 1537-6605
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2011
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
- Record Identifier
- 9984006335102771
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