TY - JOUR
T1 - 5α-reductase 2 gene mutations in three unrelated patients of Greek cypriot origin
T2 - Identification of an ancestral founder effect
AU - Skordis, Nicos
AU - Patsalis, Philippos C.
AU - Bacopoulou, Ioanna
AU - Sismani, Carolina
AU - Sultan, Charles
AU - Lumbroso, Serge
PY - 2005/3
Y1 - 2005/3
N2 - Introduction: 5α-Steroid reductase deficiency (5αSRD) is an autosomal recessive enzymatic deficiency. Mutations in the 5α-steroid reductase type 2 gene (SRD5A2) result in male pseudohermaphroditism caused by decreased dihydrotestosterone (DHT) synthesis - a key hormone of virilization of male external genitalia. Aim: To study for the first time patients from the Greek Cypriot population, describe their clinical characteristics, and identify the genetic mutations of the SRD5A2 gene. Patients and methods: Three unrelated patients with 46,XY karyotype born with ambiguous genitalia were examined. Patient 1 was raised as a girl and was diagnosed with partial androgen insensitivity syndrome, based on the clinical picture and incomplete laboratory investigation at the age of 4 years, and underwent gonadectomy. For this patient sequencing analysis of all five exons of the SRD5A2 gene and exons 2 to 8 of the androgen receptor (AR) gene was performed. Patients 2 and 3 were also born with ambiguous genitalia. The hCG test for these two patients was informative of 5αSRD, as it showed elevated T/DHT ratio after stimulation. Despite genetic counseling, both families decided to raise their infants as females because of severe undervirilization. Sequencing of the SRD5A2 gene was also completed for both patients. Results: No mutations were found in the AR sequence for patient 1. Patients 1 and 3 were found homozygous for the mutation A/G at splice junction intron 1/exon 2 and patient 2 was found heterozygous for the same A/G substitution and also heterozygous for an additional mutation, Pro181Leu, in exon 3. Conclusions: The same mutation in the SRD5A2 gene was identified in three unrelated patients, in both homozygous and heterozygous form. This splice mutation was previously reported in Turkish patients. This underlying genetic abnormality may be characteristic for the Eastern Mediterranean region and is likely due to an ancestor effect.
AB - Introduction: 5α-Steroid reductase deficiency (5αSRD) is an autosomal recessive enzymatic deficiency. Mutations in the 5α-steroid reductase type 2 gene (SRD5A2) result in male pseudohermaphroditism caused by decreased dihydrotestosterone (DHT) synthesis - a key hormone of virilization of male external genitalia. Aim: To study for the first time patients from the Greek Cypriot population, describe their clinical characteristics, and identify the genetic mutations of the SRD5A2 gene. Patients and methods: Three unrelated patients with 46,XY karyotype born with ambiguous genitalia were examined. Patient 1 was raised as a girl and was diagnosed with partial androgen insensitivity syndrome, based on the clinical picture and incomplete laboratory investigation at the age of 4 years, and underwent gonadectomy. For this patient sequencing analysis of all five exons of the SRD5A2 gene and exons 2 to 8 of the androgen receptor (AR) gene was performed. Patients 2 and 3 were also born with ambiguous genitalia. The hCG test for these two patients was informative of 5αSRD, as it showed elevated T/DHT ratio after stimulation. Despite genetic counseling, both families decided to raise their infants as females because of severe undervirilization. Sequencing of the SRD5A2 gene was also completed for both patients. Results: No mutations were found in the AR sequence for patient 1. Patients 1 and 3 were found homozygous for the mutation A/G at splice junction intron 1/exon 2 and patient 2 was found heterozygous for the same A/G substitution and also heterozygous for an additional mutation, Pro181Leu, in exon 3. Conclusions: The same mutation in the SRD5A2 gene was identified in three unrelated patients, in both homozygous and heterozygous form. This splice mutation was previously reported in Turkish patients. This underlying genetic abnormality may be characteristic for the Eastern Mediterranean region and is likely due to an ancestor effect.
KW - 5α-reductase
KW - Male pseudohermaphroditism
KW - SRD5A2 gene
UR - http://www.scopus.com/inward/record.url?scp=15844374509&partnerID=8YFLogxK
M3 - Article
C2 - 15813602
AN - SCOPUS:15844374509
SN - 0334-018X
VL - 18
SP - 241
EP - 246
JO - Journal of Pediatric Endocrinology and Metabolism
JF - Journal of Pediatric Endocrinology and Metabolism
IS - 3
ER -