ILDR1: Novel mutation and a rare cause of congenital deafness in the Saudi Arabian population.

Autor: Ramzan K; Department of Genetics, King Faisal Specialist Hospital and Research Centre, P.O.Box 3354, Riyadh 11211, Saudi Arabia. Electronic address: kramzan@kfshrc.edu.sa., Taibah K; ENT Medical Centre, Riyadh 11333, Saudi Arabia., Tahir AI; Department of Genetics, King Faisal Specialist Hospital and Research Centre, P.O.Box 3354, Riyadh 11211, Saudi Arabia., Al-Tassan N; Department of Genetics, King Faisal Specialist Hospital and Research Centre, P.O.Box 3354, Riyadh 11211, Saudi Arabia., Berhan A; Department of Genetics, King Faisal Specialist Hospital and Research Centre, P.O.Box 3354, Riyadh 11211, Saudi Arabia., Khater AM; ENT Medical Centre, Riyadh 11333, Saudi Arabia., Al-Hazzaa SA; Department of Ophthalmology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Al-Owain M; Department of Medical Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia., Imtiaz F; Department of Genetics, King Faisal Specialist Hospital and Research Centre, P.O.Box 3354, Riyadh 11211, Saudi Arabia.
Jazyk: angličtina
Zdroj: European journal of medical genetics [Eur J Med Genet] 2014 May-Jun; Vol. 57 (6), pp. 253-8. Date of Electronic Publication: 2014 Apr 21.
DOI: 10.1016/j.ejmg.2014.04.004
Abstrakt: Hearing impairment is the common human sensorineural disorder and is a genetically heterogeneous phenotype for which more than 100 genomic loci have been mapped so far. ILDR1 located on chromosome 3q13.33, encodes a putative transmembrane receptor containing an immunoglobulin-like domain. We used a combination of autozygosity mapping and candidate gene sequencing to identify a novel mutation in ILDR1, as a causative gene for autosomal-recessive non-syndromic hearing loss (arNSHL) in a consanguineous Saudi family with three affected children. Autozygosity mapping identified a shared region between the affected individuals encompassing ILDR1 on chromosome 3q13.12-3q22.1. Sequencing revealed homozygous 9 base pair duplication, resulting in an in-frame duplication of three amino acids p.(Asn109_Pro111dup). The mutation was segregating with the disease phenotype and is predicted to be pathogenic by SIFT and PROVEAN. The identified mutation is located in the immunoglobulin-type domain of the ILDR1 protein. In silico analysis using I-TASSER server and PyMOL offers the first predictions on the structural and functional consequences of this mutation. To our knowledge, this is the first ILDR1 mutation identified in a Saudi family. Identification of ILDR1 mutation in only one of 100 Saudi familial and sporadic individuals with hearing loss suggests that this mutation is unique to this family and that ILDR1 should be considered as a rare cause of congenital deafness among Saudi Arabian population. Our data also confirms the evidence for ILDR1 allelic heterogeneity and expands the number of familial arNSHL-associated ILDR1 gene mutations.
(Copyright © 2014 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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