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

Nat Genet. 1996 Apr;12(4):424-6. doi: 10.1038/ng0496-424.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chromosome Mapping
  • Chromosomes, Human, Pair 7 / genetics*
  • Deafness / congenital
  • Deafness / etiology
  • Deafness / genetics*
  • Female
  • Genetic Linkage
  • Genetic Markers
  • Goiter / etiology
  • Goiter / genetics*
  • Humans
  • In Vitro Techniques
  • Iodide Peroxidase / genetics
  • Iodine / metabolism*
  • Male
  • Pedigree
  • Syndrome
  • Thyroglobulin / genetics
  • Thyroid Gland / metabolism*


  • Genetic Markers
  • Thyroglobulin
  • Iodine
  • Iodide Peroxidase