- 作者: Sudhisha Dubey; Susan Idicula-Thomas; Mohammad Anwaruddin; Chinnaraj Saravanan; R Raveendra Varma; Anurupa Maitra
- 作者服務機構: Department of Molecular Endocrinology, National Institute for Research in Reproductive Health, Mumbai, Maharashtra, India
- 中文摘要: --
- 英文摘要:
Background:Steroid 21-hydroxylase deficiency is the most common cause of congenital adrenal hyperplasia (CAH). Detection of underlying mutations in CYP21A2 gene encoding steroid 21-hydroxylase enzyme is helpful both for confirmation of diagnosis and management of CAH patients. Here we report a novel 9-bp insertion in CYP21A2 gene and its structural and functional consequences on P450c21 protein by molecular modeling and molecular dynamics simulations methods.
Methods: A 30-day-old child was referred to our laboratory for molecular diagnosis of CAH. Sequencing of the entire CYP21A2 gene revealed a novel insertion (duplication) of 9-bp in exon 2 of one allele and a well-known mutation I172N in exon 4 of other allele. Molecular modeling and simulation studies were carried out to understand the plausible structural and functional implications caused by the novel mutation.
Results: Insertion of the nine bases in exon 2 resulted in addition of three valine residues at codon 71 of the P450c21 protein. Molecular dynamics simulations revealed that the mutant exhibits a faster unfolding kinetics and an overall destabilization of the structure due to the triple valine insertion was also observed. Conclusion: The novel 9 bp insertion in exon 2 of CYP21A2 gene significantly lowers the structural stability of P450c21 thereby leading to the probable loss of its function. - 中文關鍵字: --
- 英文關鍵字: --