title: Late diagnosis of 5alpha steroid-reductase deficiency due to IVS12A>G mutation of the SRD5a2 gene in an adolescent girl presented with primary amenorrhea.
abstract: BACKGROUND
  The clinical spectrum of 5α-reductase deficiency, caused by mutations in the SRD5A2 gene, ranges from complete female appearance of the external genitalia at birth to nearly complete male phenotype.
  
  
  METHODS
  A 14-year-old girl presented with primary amenorrhea (PA) and lack of breast development. She was 173 cm in height, had an increased amount of pubic hair and clitoromegaly (3 cm), with a 4 cm blind vaginal pouch. Gonads were palpable in the inguinal canal bilaterally and no uterus was identified on ultrasound. Chromosomal analysis showed a 46,XY karyotype. The Testosterone/DHT ratio was high (16.5) and further increased to 29.4 after stimulation with hCG, thus favouring the diagnosis of 5α-reductase deficiency. Since the issue of gender change was not considered, gonadectomy was performed followed by successful feminisation with hormonal replacement therapy.
  Molecular analysis of the SRD5A2 gene by DNA sequencing of all 5 exons revealed the presence of the splice mutation A>G at position -2 of the acceptor site of intron 1/exon 2 (IVS1-2A>G) in homozygosity. Both non-consanguineous parents were found to be heterozygotes for this mutation.
  
  
  CONCLUSIONS
  Although rare, SRD5A2 gene defect should be suspected in any girl presenting with PA and virilisation at puberty. The IVS1-2A>G mutation of the SRD5A2 gene predominates in Greek-Cypriot patients with 5α-reductase deficiency and very likely reflects a founder effect.
authors: Pediatric Endocrine Unit, Makarios Hospital, Nicosia, Department of Molecular Genetics Function & Therapy, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus. nskordis@cytanet.com.cy
authors: Nicos
authors: N
authors: Skordis
authors: Christos
authors: C
authors: Shammas
authors: Elisavet
authors: E
authors: Efstathiou
authors: Amalia
authors: A
authors: Sertedaki
authors: Vassos
authors: V
authors: Neocleous
authors: Leonidas
authors: L
authors: Phylactou
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000172:deficiency / Q000235:genetics*; D000293:Adolescent; D000568:Amenorrhea / Q000175:diagnosis* / Q000235:genetics; D001483:Base Sequence; D057210:Delayed Diagnosis; D058490:Disorder of Sex Development, 46,XY / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D020125:Mutation, Missense; D022821:RNA Splice Sites / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D022821:RNA Splice Sites; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548468:SRD5A2 protein, human