Identification of SLC26A4 c.919-2A>G compound heterozygosity in hearing-impaired patients to improve genetic counseli
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RESEARCH
Open Access
Identification of SLC26A4 c.919-2A>G compound heterozygosity in hearing-impaired patients to improve genetic counseling Qi Li1, Qing-wen Zhu2, Yong-yi Yuan2,3, Sha-sha Huang2,3, Dong-yi Han2, De-liang Huang2 and Pu Dai2,3*
Abstract Background: Mutations in the SLC26A4 gene, which encodes the anion transporter, pendrin, are a major cause of autosomal recessive non-syndromic hearing loss (NSHL) in some Asian populations. SLC26A4 c.919-2A>G (IVS7-2A>G) is the most common mutation in East Asian deaf populations. To provide a basis for improving the clinical diagnosis of deaf patients, we evaluated 80 patients with the SLC26A4 c.919-2A>G monoallelic mutation from 1065 hearing-impaired subjects and reported the occurrence of a second mutant allele in these patients. Methods: The occurrence of a second mutant allele in these 80 patients with a single c.919-2A>G mutation was investigated. Mutation screening was performed by bidirectional sequencing in SLC26A4 exons 2 to 6 and 9 to 21. Results: We found that 47/80 patients carried another SLC26A4 c.919-2A>G compound mutation. The five most common mutations were: p.H723R, p.T410M, 15+5G>A (c.1705+5G>A), p.L676Q and p.N392Y. We found a Chinese-specific SLC26A4 mutation spectrum and an associated SLC26A4 contribution to deafness. Conclusion: Our study illustrates that mutation analysis of other SLC26A4 exons should be undertaken in deaf patients with a single heterozygous SLC26A4 mutation. Moreover, a model of compound heterozygosity may partially explain the disease phenotype.
Background Hearing loss is the most prevalent form of sensory impairment in humans. Approximately 1 in 1,000 children are born with hearing loss severe enough to require special education services [1]. Deafness in at least half of all infants with profound hearing loss can be attributed to genetic factors; of these, nonsyndromic recessive causes comprise approximately 75–80% [1]. The gap junction beta-2 (GJB2) gene, which encodes connexin 26 (a component of gap junctions), is the most common cause of sensorineural hearing loss (SNHL). Mutations in the GJB2 gene are responsible for about 50% of recessively-inherited hearing loss in many populations [2]. The SLC26A4 gene, which encodes pendrin, is the second leading cause of autosomal recessive deafness characterized * Correspondence: [email protected] 2 Department of Otolaryngology - Head and Neck Surgery, PLA General Hospital, Beijing 100853, China 3 Department of Otolaryngology - Head and Neck Surgery, Hainan Branch of PLA General Hospital, Sanya 572000, China Full list of author information is available at the end of the article
by congenital deafness or progressive pre- or postlingual hearing impairment [3-6]. The SLC26A4 gene is composed of 21 exons within 2343-bp cDNA on chromosome 7q22q31 [7]. Mutations in the SLC26A4 gene are found in not only patients with Pendred syndrome (PS; OMIM # 274600), but also in individuals afflicted with nonsyndromic hearing loss (NSHL) with enlarged vestibular aqueduct (EVA) at the DFNB4
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