title: Five novel mutations of SRD5A2 found in eight Chinese patients with 46,XY disorders of sex development.
abstract: Individuals with male karyotype (46,XY) affected by 5α-reductase type 2 deficiency, a rare autosomal recessive inherited disorder, can have an almost female phenotype or partially virilized external genitalia. Mutations in the steroid-5-α-reductase (SRD5A2) gene, leading to functional impairment of 5α-reductase type 2, are responsible for this disorder. Our present study analyzed SRD5A2 gene mutations in eight unrelated 46,XY Chinese patients with disorders of sex development. Direct sequencing of genomic DNA for SRD5A2 gene revealed the presence of one homozygous (p.Q6X) and seven compound heterozygous mutations (p.G203S/R227Q, p.L20P/R227Q, p.Q6X/p.A228V, p.C222Ffs232X/p.R246Q, p.W140X/F219Sfs278X, p.Q71X/L185Tfs192X and p.Q6X/p.N193S) in our patients. Among them, p.C222Ffs232X, p.A228V, p.Q71X, L185Tfs192X and p.W140X mutations have not been previously reported. These novel mutations may provide us new insights into the molecular mechanism of 5α-reductase type 2 deficiency. Seven out of eight patients had at least one variant in exon 4, and 8 of 12 (66.7%) mutations were located in exon 4. The expanded mutation database of the SRD5A2 gene should benefit patients in the diagnosis and treatment of this disease.
authors.affiliation: Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuai Fuyuan 1#, Dongcheng District, Beijing 100730, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Nie
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.forename: Jiangfeng
authors.initials: J
authors.lastname: Mao
authors.forename: Shuangyu
authors.initials: S
authors.lastname: Lu
authors.forename: Xueyan
authors.initials: X
authors.lastname: Wu
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D058490:Disorder of Sex Development, 46,XY / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D055815:Young Adult
chemical_list: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase