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http://purl.uniprot.org/citations/19158199http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19158199http://www.w3.org/2000/01/rdf-schema#comment"

Context

The prevalence of congenital hypothyroidism (CH) associated with mutations in the TSH receptor gene (TSHR) has not been established.

Objective

We examined the frequency of TSHR mutations among patients with permanent primary CH and in the general population in Japan.

Subjects and methods

We enrolled 102 patients with permanent primary CH [70 with "moderate to severe CH" (TSH, >or=10 mU/liter) and 32 with "mild CH" (TSH, 5-10 mU/liter)], who were identified through newborn screening among 353,000 newborns born in Kanagawa prefecture from October 1979 to June 2006. These subjects were tested for TSHR mutations by PCR-based direct sequencing. We further characterized molecular functions of identified mutant TSHRs in vitro.

Results

We found three patients with moderate to severe CH who had biallelic mutations in TSHR and three patients with mild CH who had monoallelic mutations. Observed mutations included one previously characterized mutation (p.R450H) and three uncharacterized mutations (p.G132R, p.A204V, and p.D403N). In vitro experiments confirmed loss of functions of these four mutants. Among four mutations, p.R450H was particularly frequent: six of nine mutant alleles harbored p.R450H. All six alleles with p.R450H commonly carried a minor single nucleotide polymorphism, suggesting a founder effect. We estimated the prevalence of biallelic TSHR mutations to be 4.3% (three in 70) in Japanese patients with moderate to severe CH, and 1 in 118,000 (three in 353,000) in the general Japanese population.

Conclusions

In Japan, TSHR mutations are relatively common among patients with CH, and a founder mutation (p.R450H) accounts for about 70% of mutants."xsd:string
http://purl.uniprot.org/citations/19158199http://purl.org/dc/terms/identifier"doi:10.1210/jc.2008-1767"xsd:string
http://purl.uniprot.org/citations/19158199http://purl.uniprot.org/core/author"Abe Y."xsd:string
http://purl.uniprot.org/citations/19158199http://purl.uniprot.org/core/author"Hasegawa T."xsd:string
http://purl.uniprot.org/citations/19158199http://purl.uniprot.org/core/author"Adachi M."xsd:string
http://purl.uniprot.org/citations/19158199http://purl.uniprot.org/core/author"Yasui M."xsd:string
http://purl.uniprot.org/citations/19158199http://purl.uniprot.org/core/author"Asakura Y."xsd:string
http://purl.uniprot.org/citations/19158199http://purl.uniprot.org/core/author"Narumi S."xsd:string
http://purl.uniprot.org/citations/19158199http://purl.uniprot.org/core/author"Muroya K."xsd:string
http://purl.uniprot.org/citations/19158199http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19158199http://purl.uniprot.org/core/name"J Clin Endocrinol Metab"xsd:string
http://purl.uniprot.org/citations/19158199http://purl.uniprot.org/core/pages"1317-1323"xsd:string
http://purl.uniprot.org/citations/19158199http://purl.uniprot.org/core/title"TSHR mutations as a cause of congenital hypothyroidism in Japan: a population-based genetic epidemiology study."xsd:string
http://purl.uniprot.org/citations/19158199http://purl.uniprot.org/core/volume"94"xsd:string
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