2012-12-01
Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement
Publication
Publication
Nature Genetics , Volume 44 - Issue 12 p. 1375- 1381
Congenital central hypothyroidism occurs either in isolation or in conjunction with other pituitary hormone deficits. Using exome and candidate gene sequencing, we identified 8 distinct mutations and 2 deletions in IGSF1 in males from 11 unrelated families with central hypothyroidism, testicular enlargement and variably low prolactin concentrations. IGSF1 is a membrane glycoprotein that is highly expressed in the anterior pituitary gland, and the identified mutations impair its trafficking to the cell surface in heterologous cells. Igsf1-deficient male mice show diminished pituitary and serum thyroid-stimulating hormone (TSH) concentrations, reduced pituitary thyrotropin-releasing hormone (TRH) receptor expression, decreased triiodothyronine concentrations and increased body mass. Collectively, our observations delineate a new X-linked disorder in which loss-of-function mutations in IGSF1 cause central hypothyroidism, likely secondary to an associated impairment in pituitary TRH signaling.
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| doi.org/10.1038/ng.2453, hdl.handle.net/1765/57094 | |
| Nature Genetics | |
| Organisation | Erasmus School of Economics |
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Sun, Y., Bak, B., Schoenmakers, N., van Trotsenburg, P., Oostdijk, W., Voshol, P., … Bernard, D. (2012). Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement. Nature Genetics, 44(12), 1375–1381. doi:10.1038/ng.2453 |
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