Journal article
Functional differences of the PDS gene product are associated with phenotypic variation in patients with Pendred syndrome and non-syndromic hearing loss (DFNB4)
Human molecular genetics, Vol.9(11), pp.1709-1715
07/01/2000
DOI: 10.1093/hmg/9.11.1709
PMID: 10861298
Abstract
The PDS gene encodes a transmembrane protein, known as pendrin, which functions as a transporter of iodide and chloride. Mutations in this gene are responsible for Pendred syndrome and autosomal recessive non-syndromic hearing loss at the DFNB4 locus on chromosome 7q31. A screen of 20 individuals from the midwestern USA with non-syndromic hearing loss and dilated vestibular aqueducts identified three people (15%) with PDS mutations. To determine whether PDS mutations in individuals with Pendred syndrome differ functionally from PDS mutations in individuals with non-syndromic hearing loss, we compared three common Pendred syndrome allele variants (L236P, T416P and E384G), with three PDS mutations reported only in individuals with non-syndromic hearing loss (V480D, V653A and I490L/G497S). The mutations associated with Pendred syndrome have complete loss of pendrin-induced chloride and iodide transport, while alleles unique to people with DFNB4 are able to transport both iodide and chloride, albeit at a much lower level than wild-type pendrin. We hypothesize that this residual level of anion transport is sufficient to eliminate or postpone the onset of goiter in individuals with DFNB4. We propose a model for pendrin function in the thyroid in which pendrin transports iodide across the apical membrane of the thyrocyte into the colloid space.
Details
- Title: Subtitle
- Functional differences of the PDS gene product are associated with phenotypic variation in patients with Pendred syndrome and non-syndromic hearing loss (DFNB4)
- Creators
- Daryl A Scott - Howard Hughes Medical Institute and the Department of Pediatrics, University of Iowa Hospitals and Clinics and Iowa City Veterans Affairs, 52242, USARong WangTrisha M KremanMike AndrewsJoshua M McDonaldJefrey R BishopRichard J H SmithLawrence P KarniskiVal C Sheffield
- Resource Type
- Journal article
- Publication Details
- Human molecular genetics, Vol.9(11), pp.1709-1715
- Publisher
- England
- DOI
- 10.1093/hmg/9.11.1709
- PMID
- 10861298
- ISSN
- 0964-6906
- eISSN
- 1460-2083
- Grant note
- DK47881 / NIDDK NIH HHS R01-DC02842 / NIDCD NIH HHS
- Language
- English
- Date published
- 07/01/2000
- 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; Medical Genetics and Genomics; Nephrology; Otolaryngology; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9984007174702771
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