title: Congenital primary hypothyroidism in a turkish family caused by a homozygous nonsense mutation (R609X) in the thyrotropin receptor gene.
abstract: Congenital primary hypothyroidism can be caused by reduced or absent responsiveness of the thyroid gland to thyrotropin (TSH), which normally binds to the thyrotropin receptor (TSHR) and exerts its effects mainly by stimulating intracellular cyclic adenosine monophosphate (cAMP). So far 22 causative loss-of-function mutations in the TSHR gene have been reported as occurring in families from different ethnic and geographical origins. We here report a family of Turkish origin in which all four children were diagnosed as having congenital primary hypothyroidism. A homozygous nonsense mutation in codon 609 (R609X) of the TSHR gene was identified in all affected individuals as the underlying molecular defect. The mutation leads to a truncated TSHR, which is likely to be biologically inactive. This mutation has been identified before to cause resistance to TSH in a large Bedouin kindred where two affected hypothyroid individuals were also resistant to adrenocorticotrophic hormone (ATCH). Interestingly none of the affected individuals in our family had symptoms consistent with hypocortisolism, which excludes a direct impact of this TSHR mutation on the hypothalamicpituitary-adrenal axis.
authors.affiliation: University Children's Hospital, Essen, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Richter-Unruh
authors.forename: Berthold P
authors.initials: BP
authors.lastname: Hauffa
authors.forename: Nicole
authors.initials: N
authors.lastname: Pfarr
authors.forename: Joachim
authors.initials: J
authors.lastname: Pohlenz
mesh_terms: D000595:Amino Acid Sequence; D018912:Arabs / Q000235:genetics; D001120:Arginine; D001483:Base Sequence; D018389:Codon, Nonsense; D003409:Congenital Hypothyroidism; D005260:Female; D006720:Homozygote; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics*; D007231:Infant, Newborn; D008297:Male; D010375:Pedigree; D011989:Receptors, Thyrotropin / Q000235:genetics*; D014421:Turkey
chemical_list: D018389:Codon, Nonsense; D011989:Receptors, Thyrotropin; D001120:Arginine