TSH Receptor Mutations Among a Consanguineous Community
TSH Receptor Mutations Among a Consanguineous Community
Resistance to thyrotropin (RTSH) is a condition of impaired responsiveness of the thyroid
 gland to TSH, characterized by elevated TSH, low or normal thyroid hormone levels, and
 hypoplastic or normal-sized thyroid gland.

 The aim of the present study was to evaluate the clinical course over time,the
 genotype-phenotype association and the frequency of two different TSH-receptor (TSHR)
 mutations in a highly consanguineous population of the town of Um-El-Fahem.
Resistance to thyrotropin (RTSH) is a syndrome involving reduced sensitivity to TSH. It is
 characterized by elevated TSH, absence of goiter (normal or hypoplastic thyroid gland) and
 normal to very low levels of thyroid hormones. The TSH-receptor (TSHR) gene is located on
 chromosome 14q31 and it consists of extracellular, trans-membrane and intracellular domains.
 Mutation in the TSHR may cause either gain or loss of function of the receptor.
 Loss-of-function mutations are autosomal-recessively inherited and lead to a spectrum of
 phenotypes, ranging from mild euthyroid hyperthyrotropinemia to severe congenital
 hypothyroidism (CH). Insensitivity to TSH depends on both the severity and location of the
 TSHR mutations. Since the first report of familial euthyroid hyperthyrotropinemia caused by a
 TSHR mutation, several cases of loss-of-function mutations of the TSHR have been reported
 however only a few reports on the outcome of patients affected with TSHR mutations. Whether
 the condition of euthyroid hyperthyrotropinemia leads to clinical hypothyroidism, remains
 stable or normalizes over time has yet to be elucidated. We recently described a unique novel
 TSHR-inactivating mutation located at the third extracellular loop that preferentially
 affected the inositol phosphate (IP) pathway in three sisters of Arab-Muslim decent that
 presented with euthyroid hyperthyrotropinemia. Further analysis of the extended family
 revealed additional members with TSHR syndrome phenotype carrying two different TSHR
 mutations. All the affected subjects live in the same town. The aim of the present study was
 to evaluate the clinical course over time, the genotype-phenotype association and the
 frequency of these two different TSHR mutations among the highly consanguineous population of
 the town of Um El Fahem.
Inclusion Criteria:

 -  Subjects belonging to extended family of the index case

 Exclusion Criteria: