title: New Territory for an Old Disease: 5-Alpha-Reductase Type 2 Deficiency in Bulgaria.
abstract: Disorders/differences of sexual development (DSD) are a group of conditions, some of which can be clinically indistinguishable mainly due to their phenotypic variability. Defining the molecular basis of their wide spectrum is still in progress. The diagnosis of 5-alpha-reductase type 2 (5α-reductase-2) deficiency is difficult especially in newborns and pre-pubertal individuals, and as a result its frequency might be underestimated. In the present study, we describe the clinical characteristics and molecular defects in 3 nonrelated 5α-reductase-2 deficiency patients of Bulgarian descent. Sequencing analysis revealed the mutations p.Y188CfsX9 and p.G196S, and MLPA analysis showed a deletion of exon 1 in the SRD5A2 gene. The observed genetic substitutions were not detected in 76 additionally screened unrelated controls, but a heterozygous healthy carrier of the p.R171S mutation was found. This is the first study on the molecular basis of 5α-reductase-2 deficiency in Bulgaria. It suggests that the carrier frequency of mutations in the SRD5A2 gene might be noteworthy worldwide. There is no correlation between cultural aspects, location, and/or population size and the number of different mutations in SRD5A2 detected, and more efforts should be made to determine the prevalence of this condition in different geographic areas. Our study supports the importance of genetic testing in 46,XY DSD patients, especially in countries or regions where 5α-reductase-2 deficiency has not been reported so far.
authors.affiliation: National Genetic Laboratory, UHOG "Maichin dom", Medical University, Sofia, Bulgaria.
authors.forename: Silvia
authors.initials: S
authors.lastname: Andonova
authors.forename: Ralitsa
authors.initials: R
authors.lastname: Robeva
authors.forename: Radoslava
authors.initials: R
authors.lastname: Vazharova
authors.forename: Susanne
authors.initials: S
authors.lastname: Ledig
authors.forename: Liliana
authors.initials: L
authors.lastname: Grozdanova
authors.forename: Elisaveta
authors.initials: E
authors.lastname: Stefanova
authors.forename: Irena
authors.initials: I
authors.lastname: Bradinova
authors.forename: Tihomir
authors.initials: T
authors.lastname: Todorov
authors.forename: George
authors.initials: G
authors.lastname: Hadjidekov
authors.forename: Milko
authors.initials: M
authors.lastname: Sirakov
authors.forename: Peter
authors.initials: P
authors.lastname: Wieacker
authors.forename: Philip
authors.initials: P
authors.lastname: Kumanov
authors.forename: Alexey
authors.initials: A
authors.lastname: Savov
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000172:deficiency* / Q000235:genetics*; D002031:Bulgaria; D058490:Disorder of Sex Development, 46,XY / Q000235:genetics / Q000378:metabolism; D012734:Disorders of Sex Development / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics*; D009154:Mutation / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548468:SRD5A2 protein, human