A novel G143D mutation in the NADH-cytochrome b₅ reductase gene in an Indian patient with type I recessive hereditary methemoglobinemia

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• 作者：Prabhakar S. Kedar ; Prashant Warang ; Anita H. Nadkarni ; Roshan B. Colah ; Kanjaksha Ghosh
• 关键词：Cyanosis ; Recessive congenital methemoglobinemia ; NADH ; cytochrome b₅ reductase deficiency ; India
• 刊名：Blood Cells, Molecules, and Diseases
• 出版年：2008
• 出版时间：May-June 2008
• 年：2008
• 卷：40
• 期：3
• 页码：323-327
• 全文大小：663 K

文摘

We report a novel homozygous mutation responsible for NADH-b₅R deficiency in a family from Ratnagiri district in western India with recessive congenital methemoglobinemia (RCM) type I. The propositus was a 20-year-old female with a history of increasing cyanosis exacerbated by fever and weakness. There was no history of cardiac illness or exposure to drugs and chemicals. The methemoglobin level was 38.0 % in the propositus with 70 % reduction in NADH-b₅R activity. Spectroscopic analysis of the hemolysate showed normal peaks suggesting absence of Hb-M. There was no hemoglobin instability and G6PD activity was normal. This novel G → A homozygous mutation at codon 143 in exon 5 was identified by SSCP followed by DNA sequencing and results in a glycine to aspartic acid substitution in the cytochrome b₅ reductase protein. This mutation, which is located outside the FAD and NADH binding domain, leads to mild cyanosis. Investigations of the family members revealed that both the parents and a brother of the propositus were heterozygous for the G143D mutation.