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.
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