title: Identifying a novel mutation of CYP17A1 gene from five Chinese 17α-hydroxylase/17, 20-lyase deficiency patients.
abstract: Mutations of CYP17A1 gene could cause complete or partial, combined or isolated 17α-hydroxylase/17,20-lyase enzyme deficiencies (17OHD). We intended to investigate the CYP17A1 mutation in five unrelated patients and analyze its possible influence on phenotype of an atypical 17OHD patient presented with micropenis, hypertension and intermittent hypokalemia. Steroid hormones were assayed in these patients. A novel missense mutation (c.1169C>G, p. Thr390Arg) located in exon 7 was detected in one of the patients. Homozygous c. 985_987delinsAA, p. Tyr329fs mutation was found in two patients, while compound heterozygous mutations (c. 985_987delinsAA, p. Tyr329fs/c. 932-939 del, p. Val311fs and c. 287G>A, p. Arg96Gln/c. 985_987delinsAA, p. Tyr329fs) were found in two other patients, respectively. Then, steric model analysis of CYP17A1 showed that the novel mutation T390R changed the local structure as well as the electrostatic potential of the nearby beta sheet. Finally, site-directed mutagenesis and in vitro expression were used to analyze the activity of novel mutant CYP17A1. It indicated the T390R mutant retained part of enzyme activity, which was consistent to the clinical features. In conclusion, we identified a novel missense mutation of CYP17A1 gene from a patient with micropenis, hypertension and intermittent hypokalemia, which varied from other four patients. It also expanded our understanding of genotype-phenotype correlation of the disease.
authors.affiliation: Department of Endocrinology, Research Center of Tissue Engineering, Department of Plastic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Zuo
authors.forename: Hui
authors.initials: H
authors.lastname: Zhu
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.forename: Chao
authors.initials: C
authors.lastname: Xu
authors.forename: Xia-Juan
authors.initials: XJ
authors.lastname: Wang
authors.forename: Bing-Li
authors.initials: BL
authors.lastname: Liu
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Pan
authors.forename: Ying-Li
authors.initials: YL
authors.lastname: Lu
authors.forename: Wan-Ling
authors.initials: WL
authors.lastname: Wu
authors.forename: Ming-Dao
authors.initials: MD
authors.lastname: Chen
authors.forename: Huai-Dong
authors.initials: HD
authors.lastname: Song
authors.forename: Kai-Xiang
authors.initials: KX
authors.lastname: Cheng
authors.forename: Jie
authors.initials: J
authors.lastname: Qiao
mesh_terms: D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000208:ethnology / Q000235:genetics*; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002478:Cells, Cultured; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000502:physiology; D013254:Steroid 17-alpha-Hydroxylase / Q000737:chemistry / Q000235:genetics*; D055815:Young Adult
chemical_list: C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase