Apparent @entity154 contrasting with normal plasma XXXX levels and associated with inactivating mutations in the @entity5010 gene: are athyreosis and @entity16490 distinct entities?

@entity1 @entity1375 @entity154 @entity2036 @entity16490 @entity3745 @entity5010
Loss-of-function mutations in the TSH receptor gene ( @entity5010 ), usually leading to asymptomatic hyperthyrotropinemia, have been reported since 1995 in a total of eight pedigrees, with a pattern of transmission suggesting autosomal recessive inheritance. Although normal TSH secretion and action are not necessary for normal migration of the thyroid analage, they are essential for normal thyroid growth and function. In keeping with this concept, we report a severely @entity1375 @entity1 with a normally located but very hypoplastic and hypofunctional thyroid caused by @entity5010 loss-of-function mutations. The propositus' maternal great aunt also had apparent athyreosis. The propositus had undetectable uptake on 99mpertechnetate scintigraphy but normal plasma @entity3745 at 15 days of age. He was found to be a compound heterozygote for @entity5010 mutations, with the maternal allele carrying a splicing mutation (G to C transversion at position +3 of the donor site of intron 6) and the other allele a deletion of two @entity2036 (2 bases of codon 655 in exon 10). The great aunt's @entity5010 was normal. We also report the sex ratio of @entity1375 referred to our center since 1989 with apparent athyreosis (5 @entity1 , 7 @entity1 ) and with @entity16490 (41 @entity1 , 15 @entity1 ). We conclude that different genetic and nongenetic mechanisms for athyreosis and @entity16490 are likely, and that these two distinct entities are themselves heterogeneous. Our results further show that inactivating mutations in @entity5010 may account for some cases of apparent @entity154 and should be suspected, especially if plasma @entity3745 levels are normal.
