Thyroid Research Thyroid Research Archive Congenital

Mutations in Pendred's syndrome result in abnormal localization of the gene product in thyroid cells

(March 2003)

The background of the study. Pendrin is a protein that is important in the synthesis of thyroid hormone. Pendred's syndrome is a congenital disorder characterized by mutations in this protein; the consequences are decreased thyroid hormone production, goiter, and occasionally hypothyroidism, and also in deafness. It is inherited as an autosomal recessive trait. This study was done to determine why mutations in pendrin reduce thyroid hormone synthesis.

How the study was done. The cellular location of normal and mutant pendrin molecules was studied in animal cells using microscopic and immunologic methods.

The results of the study. Normal pendrin was found localized primarily in the outer membrane of thyroid cells. The abnormal (mutated) pendrin molecules were found inside the cells, but not on the outer membrane.

The conclusions of the study. Mutations in the gene for pendrin result in synthesis of pendrin molecules that cannot be carried to their normal site of action in the outer membrane of thyroid cells, which results in decreased activity of the pendrin molecule in thyroid hormone synthesis.

The original article. Rotman-Pikielny P, Hirschberg K, Maruvada P, Suzuki K, Royaux IE, Green ED, Kohn LD, Lippincott-Schwartz J, Yen PM. Retention of pendrin in the endoplasmic reticulum is a major mechanism for Pendred syndrone. Hum Mol Genet 2002;11:2625-33.

Thyroid Research Archive
Congenital Hypothyroidism

• March 2004
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• November 2002
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