Novel mutation (R192C) in CYB5R3 gene causing NADH-cytochrome b5 reductase deficiency in eight Indian patients associated with autosomal recessive congenital methemoglobinemia type-I

Hematology
Prabhakar KedarManisha Madkaikar

Abstract

To investigate the cause of recessive congenital methemoglobinemia (RCM) in Indian families and to identify molecular defect associated with RCM. Eight cases of RCM have been addressed to our laboratory in order to investigate the cause of cyanosis associated with genetic disorders. NADH-cytochrome b5 reductase (cytb5r) enzyme activities were measured by standard methods, and molecular analysis was performed by polymerase chain reaction (PCR) followed by DNA sequencing. The interpretation of mutation effect and the molecular modeling were performed by using specific software DEEP VIEW SWISS-PDB VIEWER and Pymol molecular graphics program. Eight index cases from four unrelated families were referred for the cause of cyanosis. All patients showed mild to moderate cyanosis without mental retardation or any neurologic abnormalities. The methemoglobin levels were in the range of 11.5-22.41% with 50-70% reduction in CYTB5R activity. Spectroscopic analysis of the hemolysate showed normal peaks suggesting the absence of Hb-M. Molecular characterization showed a novel homozygous mutation p.Arg192Cys in CYB5R3 gene is an evolutionarily conserved position located in exon 7 in all eight index cases. The substitution of Cys is located on th...Continue Reading

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