A Novel Point Mutation In The CYP21A2Gene Identified In A Chinese Han Patient With Nonclassic21-hydroxylase Deficiency

Context: Steroid of21-hydroxylase deficiency, resulting from mutations in theCYP21A2gene, amounts to95%of the cases with congenital adrenal hyperplasia.Rare and novel mutations of CYP21A2not derived from pseudogene have beenreported recently.Objective: The aim of the present study was to analyzed the functional and structuralconsequences of the novel missense mutation c.446G>C (p.R149P) of CYP21A2which detected in a femal patient suffering from nonclassic CAH.Design: We screened all the coding region of CYP21A2gene and the promoter reginin9suspected patients of21-OHD and also screened for the mutation p.R149P in300healthy control subjects. To determine the deleterious role of mutation protein, in vitroassays were performed in transiently transfected COS-7cells.Results: Genotyping indicates a heterozygous carrier of a novel CYP21A2mutation.The novel point mutation c.446G>C (p.R149P) in exon4was identified by directDNA sequencing. In vitro expression and activity assessment of the mutant p.R149Penzyme in transiently transfected COS-7cells show a residual CYP21activity of16.9%for the conversion of progesterone and23.4%for the conversion of 17-hydroxyprogesterone. Analysis in sillico further revealed changes in proteinstability.Conclusion: The p.R149P is a novel point disease-causing mutation. It is worthy ofnote that there are certain heterozygous carriers for CYP21A2mutations in patientswith clinically and biochemically diagnosed21-OHD.