Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement
Publication year
2012Author(s)
Source
Nature Genetics, 44, 12, (2012), pp. 1375-81ISSN
Publication type
Article / Letter to editor
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Organization
Human Genetics
Medical Psychology
Journal title
Nature Genetics
Volume
vol. 44
Issue
iss. 12
Page start
p. 1375
Page end
p. 81
Subject
IGMD 3: Genomic disorders and inherited multi-system disordersAbstract
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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- Academic publications [238441]
- Faculty of Medical Sciences [90373]
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