Journal Article

Functional differences of the <i>PDS</i> gene product are associated with phenotypic variation in patients with Pendred syndrome and non-syndromic hearing loss (DFNB4)

Daryl A. Scott, Rong Wang, Trisha M. Kreman, Mike Andrews, Joshua M. McDonald, Jeffrey R. Bishop, Richard J.H. Smith, Lawrence P. Karniski and Val C. Sheffield

in Human Molecular Genetics

Volume 9, issue 11, pages 1709-1715
Published in print July 2000 | ISSN: 0964-6906
Published online July 2000 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/9.11.1709
Functional differences of the PDS gene product are associated with phenotypic variation in patients with Pendred syndrome and non-syndromic hearing loss (DFNB4)

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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.

Journal Article.  4534 words.  Illustrated.

Subjects: Genetics and Genomics

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