[From diagnosis to treatment: multiple endocrine neoplasia (MEN)].
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Humans↗
Biomedical subjects
Shinji Kosugi
Publications and source records attributed to Shinji Kosugi.
A novel six-nucleotide insertion in exon 4 of the MEN1 gene, 878insCTGCAG, in three patients with familial insulinoma and primary hyperparathyroidism.
Three Japanese patients (a man and his two sons) in a family with clinical diagnosis of familial multiple endocrine neoplasia type 1 (MEN1) suffered from insulinoma(s), primary hyperparathyroidism and pituitary microadenoma. Genomic DNA of the patients was analyzed by sequencing for the MEN1 gene and an insertion of six nucleotides, CTGCAG, in exon 4, resulting in insertion of two amino acids, Leu-Gln, after the 256th amino acid of the menin (256insLQ), was identified. CTGCAG is a palindromic sequence and repeated twice in the wild-type allele (nucleotides 879-890). It is speculated that mutations involving only exon 4 of the MEN1 gene might induce development of insulinoma(s).
Adult↗
A novel peculiar mutation in the sodium/iodide symporter gene in spanish siblings with iodide transport defect.
Previously, we reported two Spanish siblings with congenital hypothyroidism due to total failure of iodide transport. These were the only cases reported to date who received long-term iodide treatment over 10 yr. We examined the sodium/iodide symporter (NIS) gene of these patients. A large deletion was observed by long and accurate PCR using primers derived from introns 2 and 7 of the NIS gene. PCR-direct sequencing revealed a deletion of 6192 bases spanning from exon 3 to intron 7 and an inverted insertion of a 431-base fragment spanning from exon 5 to intron 5 of the NIS gene. The patients were homozygous for the mutation, and their mother was heterozygous. In the mutant, deletion of exons 3-7 was suggested by analysis using programs to predict exon/intron organization, resulting in an in-frame 182-amino acid deletion from Met(142) in the fourth transmembrane domain to Gln(323) in the fourth exoplasmic loop. The mutant showed no iodide uptake activity when transfected into COS-7 cells, confirming that the mutation was the direct cause of the iodide transport defect in these patients. Further, the mutant NIS protein was synthesized, but not properly expressed, on the cell surface, but was mostly accumulated in the cytoplasm, suggesting impaired targeting to the plasma membrane.
Adult↗
[Non-autoimmune hyperthyroidism and hyperfunctioning thyroid adenomas caused by activating mutation of the thyrotropin receptor].
Constitutively activating mutations in the TSH receptor gene have been found in various disorders. Somatic mutations were identified in autonomously functioning thyroid nodules(AFTNs) and toxic multinodular goiters(TMNGs). Germline mutations were identified in autosomal dominantly inherited non-autoimmune hyperthyroidism and sporadic congenital hyperthyroidism. Most of activating TSH receptor mutations were identified in western countries. Only one Japanese family has been reported to have an activating TSH receptor mutation. Previous very poor and insensitive study identified no somatic TSH receptor activating mutations in 45 AFTNs and TMNGs developed in Japanese. Our recent study completely reversed their observation; about half of AFTNs in Japanese had activating mutations.
Adenoma↗
[Human gene tests as laboratory medicine in the post-genome era].
Massive and systematic information on human genes and genome is accumulating with progress in the Human Genome Project. Information on the genome has a characteristic digital signal that is appropriate for high-throughput handling by computers. Therefore, the field of gene tests has a high affinity to the field of laboratory medicine. In addition, it is a important survival strategy for departments of laboratory medicine to remain at the cutting edge. We must establish an infrastructure for utilizing genome information in clinical medicine and must anticipate numerous issues. The following issues need to be addressed. 1. Online database of human gene tests (http://www.kuhp.kyoto-u.ac.jp/idennet/DB/index2.html) 2. Anonymous handling of patients' samples 3. Establishment of independent Department of Clinical Genetics 4. Education of clinical geneticists 5. Quality control of human gene tests (especially germline mutation tests) 6. Education of technicians handling human gene tests.
Clinical Laboratory Information Systems↗
[How should be the genetic medicine in the near future?].
Massive and systematic information on human genes and genome is accumulating with progress in the Human Genome Project. Information on the genome has the characteristics of a digital signal appropriate for high-throughput handing by computers. Therefore, the field of gene tests has a high affinity to the field of laboratory medicine. In addition, it is important for survival strategy by departments of laboratory medicine that stand on the edge. We have to establish an infrastructure to utilize genome information in clinical medicine while anticipating numerous issues. The following issues need to be addressed in addition to the previous report(Rinsho Byori 50: 156-160, 2002) 1. Integral system for genetic medicine. 2. Center for human germline gene tests. 3. Quality control of human gene tests. 4. Epidemiological data of germline gene tests.
Clinical Laboratory Techniques↗