[Arginine-glutamine replacement at residue 57 of NADH-cytochrome b5 reductase in Chinese hereditary methemoglobinemia]

Center for Medical Laboratory, PLA, Fuzhou General Hospital, Fuzhou 350001.

OBJECTIVE: To elucidate the molecular mechanism of NADH cytochrome b5 reductase (Cytb5R) deficiency in hereditary methemoglobinemia. METHODS: Cytb5R cDNA was cloned from white blood cells from patient with hereditary methemoglobinemia by RT-PCR method, and the genomic DNA from 3 pedigrees with hereditary methemoglobinemia were analyzed by restriction enzyme analysis. RESULTS: On sequencing the cDNA, two missense mutation were found. One is CGG-->CAG at codon 57 of exon 3, caused Arg-Gln replacement. The other is GAG-->GGG at codon 222 of exon 8. The former mutation abolishes the Msp I recognition site which was confirmed in two of three hereditary methemoglobinemia family. The latter mutation generates a recognition site for Bsi Y I. Amplification of exon 8 by PCR followed by digestion with Bsi Y I revealed no mutation in all patients from the three families. CONCLUSION: Arg57-Gln replacement is responsible for Cytb5R deficiency in the two Chinese pedigrees.

PMID: 15622768 [PubMed - in process]