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

Val C Sheffield; Zaki Kraiem; John C Beck; Darryl Nishimura; Edwin M Stone; M Salameh; O Sadeh; B Glaser

doi:10.1038/ng0496-424

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

Journal article

Peer reviewed

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

Val C Sheffield, Zaki Kraiem, John C Beck, Darryl Nishimura, Edwin M Stone, M Salameh, O Sadeh and B Glaser

Nature genetics, Vol.12(4), pp.424-426

04/1996

DOI: 10.1038/ng0496-424

PMID: 8630498

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Abstract

Exactly 100 years ago, in 1896, Pendred first described the association of congenital deafness with thyroid goitre (MM#274600). The incidence of Pendred syndrome is estimated at 7.5-10/100,000, and may be responsible for as much as 10% of hereditary deafness. The cause of the congenital deafness in Pendred syndrome is obscure, although a Mondini type malformation of the cochlea exists in some patients. 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 occurring together by chance in highly consanguineous families. An in vivo defect in thyroid iodine organification in Pendred syndrome patients has been reported. 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 DNA pooling strategy 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.

Genetic Markers

Deafness - genetics

Goiter - etiology

Humans

Iodine - metabolism

Male

Chromosome Mapping

Syndrome

Deafness - etiology

Goiter - genetics

Pedigree

Thyroglobulin - genetics

Female

Iodide Peroxidase - genetics

Chromosomes, Human, Pair 7 - genetics

Deafness - congenital

In Vitro Techniques

Thyroid Gland - metabolism

Genetic Linkage

Details

Title: Subtitle: Pendred syndrome maps to chromosome 7q21-34 and is caused by an intrinsic defect in thyroid iodine organification
Creators: Val C Sheffield - Department of Pediatrics, University of Iowa, Iowa City 52242, USA
Zaki Kraiem
John C Beck
Darryl Nishimura
Edwin M Stone
M Salameh
O Sadeh
B Glaser
Resource Type: Journal article
Publication Details: Nature genetics, Vol.12(4), pp.424-426
DOI: 10.1038/ng0496-424
PMID: 8630498
NLM abbreviation: Nat Genet
ISSN: 1061-4036
eISSN: 1546-1718
Publisher: United States
Grant note: R01HG00457 / NHGRI NIH HHS
Language: English
Date published: 04/1996
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9983979978802771

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