Abstract: Objective To detect the mutation of hemochromatosis-related gene in a patient suspected with hereditary hemochromatosis and his family members. Methods The peripheral blood samples were collected from the patient and his family members after recording patient's clinical data. The indices of iron metabolism including serum iron (SI), total iron binding capacity (TIBC), serum ferritin (SF)and transferrin saturation (TS) were determined. The genomic DNA from peripheral blood was isolated, and polymerase chain reaction (PCR) was used to amplify exon and intron splice junctions, and the 5' and 3' untranslated regions (UTRs) of HFE,HJV,HAMP,TFR2 and SLC40A1 genes. After agarose gel electrophoresis and purification, the PCR products were submitted to bidirectional sequence analysis for determining mutation. Results SF, SI and TS increased significantly in the patient. Mutation analysis in the patient revealed c.224C>T (p.Ala75Val) and c.714C>G (p.Ile238Met) heterozygous mutations respectively located in exon2 and exon5 of TFR2. Additional synonymous mutation was also found in exon6 of SLC40A1 (c.663T>C, p.Val221Val).There was no mutation being found in HFE, HAMP and HJV in the patient. SLC40A1 V221V mutation was all detected in the patient's family members, but it did not happen to the aforementioned TFR2 mutations. Conclusions TFR2 A75V and I238M mutations may be the genetic basis of hereditary hemochromatosis in this patient, but its pathogenic mechanism remains to be further studied.

Key words: Hereditary hemochromatosis, Iron overload, Transferrin receptor 2