Biomedical subjects
Publications and source records attributed to Hiroyuki Kurahachi.
We report a new Japanese family with tricho-rhino-phalangeal syndrome type III (TRPS III) who have a missense mutation (Arg908Gln) of theTRPS1 gene (TRPS1) in affected individuals of the family. This study supports the notion that TRPS III results from missense mutations in exon 6 of TRPS1.
The presence of TSH receptor antibody (TRAb) is rarely responsible for hyperthyroidism due to metastatic lesions of thyroid carcinoma. A 70-year-old woman was incidentally found to be thyrotoxic around the time that external irradiation was performed for multiple bone metastases 9 years after subtotal thyroidectomy for follicular carcinoma. Hyperthyroidism persisted after oral administration of thiamazole. Relevant laboratory data were as follows: FT4 9.6 ng/L, FT3 7.3 ng/L, TSH <0.19 mU/L, TBII 70, TSAb 735, and Tg 32,000 microg/L. 131I-total body scan showed 131I accumulation in the occipital bone, cervical vertebra, thoracic vertebra, ilium, and residual thyroid gland. Since the ilium uptake (11.6) was markedly higher compared to the residual thyroid gland uptake (0.14), four subsequent 131I therapies were performed. The patient became hypothyroid, and TBII became negative. TSAb became negative after the first 131I-therapy but has increased again to 204 at present. Tg was 1,962 microg/L despite high TSH levels. 131I accumulation in the residual thyroid, cervical vertebra, and thoracic vertebra disappeared. Also 131I accumulation in the ilium has gradually decreased, but the image in the occipital bone has become markedly distinctive. This is a rare case characterized by TRAb-positive hyperthyroidism, by T3-predominant thyrotoxicosis, and by stronger accumulation of 131I in the metastatic tumor than in the residual thyroid gland. Thus, the response to TRAb and 131I-therapy is different among metastatic thyroid tissues.
The melanocortin-4 receptor (MC4R) is a member of the seven membrane-spanning G protein-coupled receptor superfamily and signals through the activation of adenylyl cyclase. The MC4R mutations are the most common known monogenic cause of human obesity. However, no such mutations have been found in Japanese obese subjects. Here we report a novel homozygous missense mutation of MC4R (G98R) in a nondiabetic Japanese woman with severe early-onset obesity, which is located in its second transmembrane domain. Her birth weight was 3,360 g, and she gained weight progressively from 10 months of age. At 40 years of age, her weight reached 160 kg and a BMI of 62 kg/m(2). Her parents, who are heterozygous for the mutation, have BMIs of 26 and 27 kg/m(2). In vitro transient transfection assays revealed no discernable agonist ligand binding and cAMP production in HEK293 cells expressing the mutant receptor, indicating a severe loss-of-function mutation. This study represents the first demonstration of a pathogenic mutation of MC4R in Japan and will provide further insight into the pathophysiologic role of the hypothalamic melanocortin system in human obesity.
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