title: Identification of a novel mutation in CYP17A1 gene.
abstract: 17α-hydroxylase/17,20-lyase deficiency (17OHD) is a rare autosomal recessive genetic disease that is characterized by low-renin hypertension, hypokalemia, and abnormal development of the genitalia. Mutations in the CYP17A1 gene account for this disease. We aim to investigate the CYP17A1 mutation and analyze its possible influence on phenotype in a Chinese patient with 17OHD. Steroid hormones were assayed. The 8 exons of the CYP17A1 gene were amplified and directly sequenced. Wild-type and mutant CYP17A1 cDNA were cloned into pcDNA3.1 expression vectors and transfected into 293T cells. Finally, 17-hydroxylase and 17,20-lyase activity were detected by using progesterone and 17-hydroxypregnenolone as the substrates. A novel missense mutation c.716 G>A located in exon 4 that changed the amino acid from arginine to glutamine (R239Q) was discovered in the patient. Steric model analysis of CYP17A1 showed that R239Q changed the local structure and the electrostatic potential. Functional study indicated that the R239Q mutant caused the complete loss of both 17α-hydroxylase and 17,20-lyase activities. Our study expanded the CYP17A1 mutation spectrum. With a functional study, we confirmed that the novel mutation caused the complete loss of both 17α-hydroxylase and 17,20-lyase activities.
authors.affiliation: State Key Laboratory of Medical Genomics, Molecular Medical Centre, Shanghai Institute of Endocrinology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Li-Qiong
authors.initials: LQ
authors.lastname: Xue
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.forename: Li-Bo
authors.initials: LB
authors.lastname: Chen
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Pan
authors.forename: Hui
authors.initials: H
authors.lastname: Zhu
authors.forename: Bing-Li
authors.initials: BL
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Wan-Ling
authors.initials: WL
authors.lastname: Wu
authors.forename: Ming-Dao
authors.initials: MD
authors.lastname: Chen
authors.forename: Ying-Li
authors.initials: YL
authors.lastname: Lu
authors.forename: Jie
authors.initials: J
authors.lastname: Qiao
authors.forename: Huai-Dong
authors.initials: HD
authors.lastname: Song
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D002681:China; D005260:Female; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010641:Phenotype; D016415:Sequence Alignment; D013254:Steroid 17-alpha-Hydroxylase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D013254:Steroid 17-alpha-Hydroxylase