1994 Fiscal Year Final Research Report Summary
Analysis of thyrotropin (TSH) receptor gene abnormalities
| Project/Area Number |
05670870
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
内分泌・代謝学
|
|---|
| Research Institution | Nagasaki University |
|---|
Principal Investigator |
YOKOYAMA Naokata Nagasaki University School of Medicine, Assistant, 医学部, 助手 (10240219)
|
|---|
| Project Period (FY) |
1993 – 1994
|
| Keywords | TSH receptor / TSH unresponsiveness / Congenital primary hypothyroidism / TSH receptor gene |
|---|
| Research Abstract |
Congenital primary hypothyroidism due to thyrotropin (TSH) unresponsiveness is a very rare disorder and only a few cases have been documented previously. To elucidate whether structural abnormalities in the TSH receptor (TSHR) could be a primary underlying mechanism of this disorder, we analyzed nucleotide sequence of the entire coding region of the TSHR gene in three patients diagnosed with congenital primary hypothyroidism associated with TSH unresponsiveness. Diagnosis of TSH unresponsiveness was largely made based on the following criteria : (a) congenital primary hypothyroidism with autosomal recessive inheritance, (b) a nongoitrous thyroid gland in a normal position with low thyroidal radioactive iodine uptake, (c) normal in vitro TSH bioactivity or absent in vivo response to exogenous TSH,and (d) absence of thyroid autoantibodies. The TSHR cDNA was successfully obtained from RNA of peripheral mononuclear leukocytes with reverse transcription and polymerase chain reaction, and was sequenced directly. Comparison of these nucleotide sequences with the normal TSHR sequence revealed no difference in the predicted amino acid sequence with a heterozygous polymorphism in codon 601 in one patient, indicating absence of TSHR structural abnormalities in these patients. Our results indicate that congenital primary hypothyroidism associated with TSH unresponsiveness in unlikely to be due to mutations in the TSHR-structure gene.
|
