title: A novel compound heterozygous mutation in the CYP17 (P450 17alpha-hydroxylase) gene leading to 17alpha-hydroxylase/17,20-lyase deficiency.
abstract: Mutations in the CYP17 gene impair steroid biosynthesis in the adrenals and gonads and often cause 17alpha-hydroxylase/17,20-lyase deficiency, leading to amenorrhea, sexual infantilism, and hypokalemic low aldosterone hypertension. Several CYP17 mutations resulting in 17alpha-hydroxylase/17,20-lyase deficiency have been reported previously. In the present study, we found a novel CYP17 mutation from the molecular analysis of a Korean patient with primary amenorrhea with a 46,XX karyotype, and hypokalemic hypertension. We sequenced all 8 exons of the CYP17 gene that were amplified from patient's genomic DNA using polymerase chain reaction (PCR) and found a compound heterozygous mutation in the CYP17 structural gene; a 1-base deletion and a 1-base transversion (TAC-->AA) at codon 329, leading to the production of a truncated protein (1-417 amino acids), and a 3-base deletion (TCC, either 350-351 or 351-352 codon) in the other allele. Restriction enzyme digestion analysis of patient's and parental DNA showed that the 1-base deletion and the 3-base deletion are inherited from mother and father, respectively. Here we conclude that these novel compound heterozygous mutations might account for the patient's clinical manifestations of 17alpha-hydroxylase/17,20-lyase deficiency.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jong Ryeal
authors.initials: JR
authors.lastname: Hahm
authors.forename: Deok Ryong
authors.initials: DR
authors.lastname: Kim
authors.forename: Dong Kee
authors.initials: DK
authors.lastname: Jeong
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Chung
authors.forename: Myung-Shik
authors.initials: MS
authors.lastname: Lee
authors.forename: Yong-Ki
authors.initials: YK
authors.lastname: Min
authors.forename: Kwang-Won
authors.initials: KW
authors.lastname: Kim
authors.forename: Moon-Kyu
authors.initials: MK
authors.lastname: Lee
mesh_terms: D000328:Adult; D000483:Alleles; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D006973:Hypertension / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012741:Sexual Maturation / Q000235:genetics; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*
chemical_list: D004247:DNA; D013254:Steroid 17-alpha-Hydroxylase