title: CYP17A1 gene mutations and hypertension variations found in 46, XY females with combined 17α-hydroxylase/17, 20-lyase deficiency.
abstract: The aim of this study was to analyze the structural consequences of the mutations in CYP17A1 gene and their relationship with the variations of clinical manifestations in three patients who presented with complete or partial combined 17α-hydroxylase/17,20-lyase deficiency (17OHD). DNA sequences of the coding exons and intron/exon boundaries of the CYP17A1 gene were analyzed for mutations. In silico analysis with computational three-dimensional model of human P450c17 and multiple alignments analysis were performed to evaluate the spatial conformational changes by missense mutations. Five mutations p.S117fs (c.351_352delCT), p.H373L (c.1184 A>T), p.Y329fs (c.985_987delTACinsAA), p.A82D (c.245 C>A) and p.L209P (c.626 T>C) were identified in three patients, respectively. The novel mutation p.S117fs (c.351_352delCT) has not been reported previously. In silico analysis explained the conformational changes by the described mutations, which resulted in different severe 17OHD. Our studies also suggest that molecular data accompanying with in silico analysis of the CYP17A1 gene are much helpful for the diagnosis, management and genetic counseling of 17OHD.
authors.affiliation: Department of Clinical Genetics .
authors.forename: Yue-Ping
authors.initials: YP
authors.lastname: Wang
authors.forename: Yun-Jing
authors.initials: YJ
authors.lastname: Zhao
authors.forename: Guang-Yu
authors.initials: GY
authors.lastname: Zhou
authors.forename: Bing
authors.initials: B
authors.lastname: He
mesh_terms: D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People; D002681:China; D019295:Computational Biology; D003198:Computer Simulation; D003577:Cytochrome P-450 Enzyme System / Q000172:deficiency* / Q000235:genetics; D005103:Expert Systems; D005260:Female; D006061:Gonadal Dysgenesis, 46,XY / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D020125:Mutation, Missense; D011487:Protein Conformation; D016415:Sequence Alignment; D012720:Severity of Illness Index; D013254:Steroid 17-alpha-Hydroxylase / Q000737:chemistry / Q000235:genetics*; D055815:Young Adult
chemical_list: D003577:Cytochrome P-450 Enzyme System; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase
keywords: 17α-hydroxylase/17; 20-lyase deficiency; CYP17A1 gene; disorder of sex development; hypertension; mutation