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The W546X mutation of the thyrotropin receptor gene: potential major contributor to thyroid dysfunction in a Caucasian population

Jordan, Nicola, Williams, Nigel Melville, Gregory, John Welbourn, Evans, C., Owen, Michael John and Ludgate, Marian Elizabeth 2003. The W546X mutation of the thyrotropin receptor gene: potential major contributor to thyroid dysfunction in a Caucasian population. Journal of Clinical Endocrinology & Metabolism 88 (3) , pp. 1002-5. 10.1210/jc.2002-021301

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Abstract

Congenital hypothyroidism (CH) occurs in approximately 1 in 3000 births and can be caused by mutations in 9 known genes, including that encoding the TSH receptor (TSHR). We report on two Welsh siblings, detected by neonatal screening, who had normal sized and placed glands but negative isotope uptake. Genomic DNA was obtained from both siblings and parents, the TSHR amplified using pairs of intronic and/or overlapping exonic primers and the PCR products sequenced automatically. Both siblings were homozygous for a previously described G to A transition producing a missense mutation, W546X, in the fourth membrane spanning region of the TSHR, rendering it unresponsive to TSH. Both parents were heterozygous and unrelated; furthermore, the W546X has been described in three further families (one of which is Welsh), suggesting that it may be a relatively common mutation. We genotyped 368 euthyroid Welsh individuals using single nucleotide primer extension, and found 366 homozygous wild-type (G:G) and 2 heterozygous (G:A) for the mutation. In conclusion, CH in the siblings is due to the missense mutation, W546X, in their TSHR gene. The W546X allele was detected in approximately 1 in 180 individuals and may be a major contributor to hypothyroidism in the Welsh population.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Publisher: The Endocrine Society
ISSN: 0021-972X
Related URLs:
Last Modified: 04 Jun 2017 01:32
URI: http://orca-mwe.cf.ac.uk/id/eprint/403

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