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Pendred syndrome maps to chromosome 7q21-34 and is caused by an intrinsic defect in thyroid iodine organification

Nature Genetics volume 12, pages 424–426 (1996)Cite this article

Abstract

Exactly 100 years ago, in 1896, Pendred first described the association of congenital deafness with thyroid goitre (MIM#274600)1. The incidence of Pendred syndrome is estimated at 7.5–10/100,000, and may be responsible for as much as 10% of hereditary deafness2. The cause of the congenital deafness in Pendred syndrome is obscure, although a Mondini type malformation of the cochlea exists in some patients3,4. The reason for the association between the thyroid and cochlear defects is similarly obscure, leading some investigators to suggest that the two recessive defects may be occuring together by chance in highly consanguineous families. An in vivo defect in thyroid iodine organification in Pendred syndrome patients has been reported5. However, the molecular basis of this defect is unknown and the presence of an intrinsic thyroidal defect has not been conclusively demonstrated. We have adopted a genetic linkage study as a first step towards identifying the gene. The availability of an inbred Pendred syndrome kindred allowed us to utilize an efficient DMA pooling strategy6–8 to perform a genome-wide linkage search for the disease locus. In this way, we have mapped the disease locus to an approximately 9-cM interval between GATA23F5 and D7S687 on chromosome 7. In addition, we demonstrate an intrinsic thyroid iodine organification defect in a patient,s thyroid cells as the cause of the thyroid dysfunction.

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Authors and Affiliations

  1. Department of Pediatrics, Division of Medical Genetics, University of Iowa, Iowa City, Iowa, 52242, USA

    Val C. Sheffield, John C. Beck & Darryl Nishimura

  2. Department of Ophthalmology, University of Iowa, Iowa City, Iowa, 52242, USA

    Edwin M. Stone

  3. Endocrine Research Unit, Carmel Medical Center Haifa, Israel

    Zaki Kraiem & Orit Sadeh

  4. The Technion Faculty of Medicine, Haifa, Israel

    Zaki Kraiem

  5. Department of Endocrinology and Metabolism, Hadassah University Hospital, P.O. Box 12000, Jerusalem, Israel

    Muhamad Salameh & Benjamin Glaser

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  1. Val C. Sheffield
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Sheffield, V., Kraiem, Z., Beck, J. et al. Pendred syndrome maps to chromosome 7q21-34 and is caused by an intrinsic defect in thyroid iodine organification. Nat Genet 12, 424–426 (1996). https://doi.org/10.1038/ng0496-424

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