title: A novel SRD5A2 mutation with loss of function identified in Chinese patients with hypospadias.
abstract: OBJECTIVE
  To investigate the functional change of SRD5A2 gene mutations identified in patients with 5α-reductase type 2 deficiency.
  
  
  METHODS
  Three unrelated subjects born with ambiguous genitalia were included. All patients were initially reared as girls, but they gradually exhibited variable degrees of virilization at puberty without breast development, followed by a change of gender role. Sequencing analysis of the SRD5A2 gene was performed and enzymatic activities of 5α-reductase type 2 were assessed.
  
  
  RESULTS
  Three compound heterozygous mutations in the SRD5A2 gene were identified: patient 1 with p.G203S/ c.655delT, patient 2 with p.Q6X/p.G203S, and patient 3 with p.G203S/c.755_756insT. Heterozygosity for the p.V89L polymorphism was also found in patients 2 and 3. The c.655delT mutation led to a complete loss of the enzymatic activity, whereas mutants p.G203S and c.755_756insT resulted in a reduction of the enzymatic activities by 60 and 90%, respectively.
  
  
  CONCLUSIONS
  Two frameshift heterozygous mutations, c.655delT and c.755_756insT, led to a dramatic reduction in 5α-reductase activity, and the latter had not been reported previously. In addition, the heterozygous mutation (p.G203) identified in the 3 patients presumably suggests a founder effect in the Chinese population and may explain the similarity in phenotype among the patients.
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Key Laboratory of Endocrine Tumor, Shanghai Institute of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Manna
authors.initials: M
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Huijie
authors.initials: H
authors.lastname: Zhang
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Li
authors.forename: Shouyue
authors.initials: S
authors.lastname: Sun
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D044466:Asian People / Q000235:genetics; D012734:Disorders of Sex Development / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D006801:Humans; D007021:Hypospadias / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548468:SRD5A2 protein, human