Year-end Sale % OFF 
Abstract
BackgroundMutations in SLC26A4, which encodes pendrin, are a common cause of deafness. SLC26A4 mutations are responsible for Pendred syndrome and non-syndromic enlarged vestibular aqueduct (EVA). The mutation spectrum of SLC26A4 varies widely among ethnic groups. To investigate the incidence of EVA in Chinese population and to provide appropriate genetic testing and counseling to patients with SLC26A4 variants, we conducted a large-scale molecular epidemiological survey of SLC26A4.MethodsA total of 2352 unrelated non-syndromic hearing loss patients from 27 different regions of China were included. Hot spot regions of SLC26A4, exons 8, 10 and 19 were sequenced. For patients with one allelic variant in the hot spot regions, the other exons were sequenced one by one until two mutant alleles had been identified. Patients with SLC26A4 variants were then examined by temporal bone computed tomography scan for radiological diagnosis of EVA. Ten SLC26A4 variants were cloned for functional study. Confocal microscopy and radioisotope techniques were used to examine the membrane expression of pendrin and transporter function.ResultsOf the 86 types of variants found, 47 have never been reported. The ratio of EVA in the Chinese deaf population was at least 11%, and that in patients of Han ethnicity reached at least 13%. The mutational spectrum and mutation detection rate of SLC26A4 are distinct among both ethnicities and regions of Mainland China. Most of the variants caused retention of pendrin in the intracellular region. All the mutant pendrins showed significantly reduced transport capability.ConclusionAn overall description of the molecular epidemiological findings of SLC26A4 in China is provided. The functional assessment procedure can be applied to identification of pathogenicity of variants. These findings are valuable for genetic diagnosis, genetic counseling, prenatal testing and pre-implantation diagnosis in EVA families.
Highlights
SLC26A4 encodes an anion transporter transmembrane protein, pendrin, which is expressed in the thyroid, kidney, and cochlea [1]
Pendrin is a member of the anion transporter family SLC26, which mediates the exchange of anions including Cl, HCO3, OH, I, or formate [2]
The missense variants accounted for 60.76% (48/79, excluding the untranslated region (UTR) variant and intron variants) of all the SLC26A4 variants
Summary
SLC26A4 encodes an anion transporter transmembrane protein, pendrin, which is expressed in the thyroid, kidney, and cochlea [1]. Pendrin is a member of the anion transporter family SLC26, which mediates the exchange of anions including Cl-, HCO3-, OH-, I-, or formate [2]. Located pendrin seems to be responsible for the efflux of iodide into the follicular lumen [3]. Pendrin is suspected to mediate Cl2/HCO3- exchange in the acid–base regulating B- and non-A–non-B-intercalated cells [4]. In the inner ear, pendrin is thought to mediate Cl2/HCO3- exchange, and is involved in the conditioning of endolymphatic fluid, presumably due to HCO3-. Mutations in SLC26A4, which encodes pendrin, are a common cause of deafness. SLC26A4 mutations are responsible for Pendred syndrome and non-syndromic enlarged vestibular aqueduct (EVA). To investigate the incidence of EVA in Chinese population and to provide appropriate genetic testing and counseling to patients with SLC26A4 variants, we conducted a large-scale molecular epidemiological survey of SLC26A4
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
