Five novel mutations of SRD5A2 found in eight Chinese patients with 46,XY disorders of sex development

• Published in: Molecular human reproduction Vol. 17; no. 1-2; pp. 57 - 62
• Main Authors: Nie, Min, Zhou, Qi, Mao, Jiangfeng, Lu, Shuangyu, Wu, Xueyan
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 2011
• Subjects: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase - genetics; 46, XY Disorders of Sex Development - genetics; Adolescent; Adult; Asian Continental Ancestry Group - genetics; Biological and medical sciences; Child; Child, Preschool; Embryology: invertebrates and vertebrates. Teratology; Female; Fundamental and applied biological sciences. Psychology; Humans; Infant; Male; Mutation; Young Adult; Asia; China; Human; 5α-reductase type 2 deficiency; SRD5A2; Enzyme; Deficiency; Sex; Sexual differentiation disorder; Developmental disorder; ambiguous genitalia; Genital diseases; 46,XY disorders of sex development; Gene; Chinese; gene mutations; Oxidoreductases; Mutation; Reductase
• ISSN: 1360-9947; 1460-2407
• DOI: 10.1093/molehr/gaq072

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.