PubMed:15749661 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/15749661","sourcedb":"PubMed","sourceid":"15749661","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/15749661","text":"Two novel mutations, L490R and V561X, of the transferrin receptor 2 gene in Japanese patients with hemochromatosis.\nBACKGROUND AND OBJECTIVES: The low prevalence of the C282Y mutation of the HFE gene in Japan means that the genetic background of hemochromatosis in Japanese patients remains unclear. In a previous report, we showed that 3 patients from one family had an AVAQ 594-597 deletion of the transferrin receptor (TfR2) gene. This suggests that the TfR2 gene is involved in hemochromatosis in Japanese patients.\nDESIGN AND METHODS: Nine patients clinically diagnosed with hemochromatosis were included in the study. DNA was extracted from whole blood samples collected with informed consent. The HFE and TfR2 genes were analyzed by sequencing the coding region and splicing sites.\nRESULTS: There were no mutations in the HFE gene. In the TfR2 gene, 2 novel mutations, 1469T-\u003eG (L490R) and 1665delC (V561X), were found in 2 patients. A known variation, 714C-\u003e (I238M), was also found in the patient with L490R. The patient homozygous for both L490R and I238M presented with a mild manifestation of hemochromatosis at the age of 41 years. His liver was cirrhotic with parenchymal iron deposits and the result of a glucose tolerance test was compatible with diabetes mellitus. The patient homozygous for V561X had severe iron overload with the triad of cirrhosis, diabetes mellitus and skin pigmentation at the age of 58 years.\nINTERPRETATION AND CONCLUSIONS: Taken together with the previous report, 5 of our 12 patients with hemochromatosis manifesting in middle age had mutations in the TfR2 gene. Thus, TfR2 plays a role in the pathogenesis of hemochromatosis in 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