title: Identification of five novel STAR variants in ten Chinese patients with congenital lipoid adrenal hyperplasia.
abstract: Congenital lipoid adrenal hyperplasia (CLAH) is a rare autosomal recessive disorder caused by defective synthesis of all steroids. This disorder is characterized by 46,XY sex reversal, skin hyperpigmentation, early-onset adrenal crisis and enlarged adrenal with fatty accumulation. CLAH is caused by mutations in the STAR gene. The clinical features and STAR gene mutation spectrum of a large cohort of Chinese patients with CLAH were not reported previously. We performed clinical retrospective review and genetic analysis of the STAR gene in ten unrelated Chinese phenotypic female patients who were clinically diagnosed with CLAH and followed up in our hospital from 2006 to 2015. All ten patients, including two 46,XY females and eight 46,XX females, presented skin hyperpigmentation and early salt-wasting episode, and showed normal growth and development after steroid replacement treatment. Totally 20 mutant alleles containing 11 different STAR gene mutations were identified in these ten patients, including five novel variants (two missense and three null variants), all predicted to be pathogenic in bioinformatics analysis, and six mutations described in previous literature. Among these 11 mutations, a reported mutation c.772C>T and a novel variant c.707_708delinsCTT were most frequent, accounting for 35% and 15% of the total mutant alleles, respectively. This is the first report of a large Chinese cohort with CLAH, presenting the mutation spectrum of the STAR gene and two possible founder mutations in the Chinese population, which may contribute to better genetic counseling and prenatal diagnosis.
authors.affiliation: Department of Pediatric Endocrinology/Genetics, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai 200092, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Pediatric Endocrinology/Genetics, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai 200092, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Pediatric Endocrinology/Genetics, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai 200092, China.
authors.forename: Lianshu
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Pediatric Endocrinology/Genetics, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai 200092, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Qiu
authors.affiliation: Department of Pediatric Endocrinology/Genetics, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai 200092, China.
authors.forename: Huiwen
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pediatric Endocrinology/Genetics, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai 200092, China.
authors.forename: Yongguo
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Pediatric Endocrinology/Genetics, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai 200092, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Pediatric Endocrinology/Genetics, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai 200092, China.
authors.forename: Zhuwen
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Department of Pediatric Endocrinology/Genetics, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai 200092, China. Electronic address: gu_xuefan@163.com.
authors.forename: Xuefan
authors.initials: X
authors.lastname: Gu
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D044466:Asian People / Q000235:genetics*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D058490:Disorder of Sex Development, 46,XY / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008958:Models, Molecular; D009154:Mutation; D020125:Mutation, Missense; D011487:Protein Conformation
chemical_list: D002352:Carrier Proteins
keywords: Congenital lipoid adrenal hyperplasia; Mutation spectrum; STAR gene; Steroidogenic acute regulatory protein