NADH‐cytochrome b5 reductase 3 deficiency is an important genetic cause of recessive congenital methemoglobinemia (RCM) and occurs worldwide in autosomal recessive inheritance. In this Mutation Update, we provide a comprehensive review of all the pathogenic mutations and their molecular pathology in RCM along with the molecular basis of RCM in 21 new patients from the Indian population, including four novel variants: c.103A>C (p.Thr35Pro), c.190C>G (p.Leu64Val), c.310G>T (p.Gly104Cys), and c.352C>T (p.His118Tyr). In this update, over 78 different variants have been described for RCM globally. Molecular modeling of all the variants reported in CYB5R3 justifies association with the varying severity of the disease. The majority of the mutations associated with the severe form with a neurological disorder (RCM Type 2) were associated with the FAD‐binding domain of the protein while the rest were located in another domain of the protein (RCM Type 1).

中文翻译：

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突变更新：隐性先天性高铁血红蛋白血症中CYB5R3基因的变异

NADH-细胞色素b 5还原酶3缺乏是隐性先天性高铁血红蛋白血症（RCM）的重要遗传原因，并且在全球以常染色体隐性遗传方式发生。在本突变更新中，我们对RCM中的所有致病性突变及其分子病理学以及RCM的分子基础进行了全面的综述，其中包括来自印度人口的21名新患者，包括四个新的变异体：c.103A> C（p。 Thr35Pro），c.190C> G（p.Leu64Val），c.310G> T（p.Gly104Cys）和c.352C> T（p.His118Tyr）。在此更新中，已经为全球描述了超过78种不同的RCM变体。CYB5R3中报道的所有变异的分子模型证明与疾病的严重程度相关。与严重形式的神经系统疾病相关的突变（RCM 2型）与该蛋白的FAD结合结构域相关，而其余突变位于该蛋白的另一结构域（RCM 1型）中。