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Mutation update: Variants of the CYB5R3 gene in recessive congenital methemoglobinemia
Author(s) -
Gupta Vinod,
Kulkarni Anuja,
Warang Prashant,
Devendra Rati,
Chiddarwar Ashish,
Kedar Prabhakar
Publication year - 2020
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23973
Subject(s) - biology , genetics , mutation , gene , methemoglobinemia , population , molecular genetics , medicine , biochemistry , environmental health
NADH‐cytochrome b 5 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).