The coexistence of a novel inactivating mutant thyrotropin receptor allele with two XXXX mutations: a genotype-phenotype correlation.

@entity1 @entity1375 @entity5787 @entity72825 @entity72828 @entity72821 @entity72827 @entity72822 @entity72824 @entity5010 @entity72823 @entity72826
CONTEXT: @entity5010 ( @entity5010 ) and @entity5787 ( @entity5787 ) gene mutations occur independently. This is the first report of their coexistence in the same individuals. OBJECTIVES: The objective of the study was to evaluate the genotype-phenotype correlations when mutations in both genes are present alone or together in the same individual. @entity1 AND METHODS: Thirty subjects from an extended Arab kindred underwent clinical investigation and molecular studies of the mutant TSHRs. RESULTS: A novel mutant @entity5010 was identified, involving four nucleotides at three sites on the same allele, @entity72821 ( @entity72822 ), @entity72823 ( @entity72824 ), and @entity72825 ( @entity72826 ). In addition, two known @entity5787 gene mutations, @entity72827 and @entity72828 , were identified. Thirteen heterozygotes for the mutant @entity5010 allele had mild hyperthyrotropinemia. In nine of theses, the coexistence of a @entity5787 mutation in one allele did not magnify the hyperthyrotropinemia. Homozygotes for the mutant @entity5010 and a compound heterozygote for the @entity5787 mutations presented @entity1375 . In vitro studies showed increasing loss of function for @entity72824 less than @entity72826 less than @entity72824 / @entity72826 @entity5010 mutants, the latter being that expressed in the subjects under investigation. The two interchangeably used WT @entity5010 vectors, L87 and V87, although functionally identical, differed in structure and function in the presence of the @entity72824 mutation. CONCLUSIONS: @entity5010 and @entity5787 gene mutations were identified alone and together in individuals of a consanguineous kindred. Homozygotes for the @entity5010 and a compound heterozygote for the @entity5787 mutations were @entity1375 . The mild hyperthyrotropinemia of heterozygotes for the mutant @entity5010 allele was not aggravated by the coexistence of a @entity5787 defect in one allele.
