TY  - JOUR
TI  - Mutations in AR or SRD5A2 Genes: Clinical Findings, Endocrine
Pitfalls, and Genetic Features of Children with 46,XY DSD
AB  - Objective: Androgen insensivity syndrome (AIS) and 5α-reductase deficiency (5α-RD) present with indistinguishable phenotypes
among the 46,XY disorders of sexual development (DSD) that usually necessitate molecular analyses for the definitive diagnosis in the
prepubertal period. The aim was to evaluate the clinical, hormonal and genetic findings of 46,XY DSD patients who were diagnosed as
AIS or 5α-RD.
Methods: Patients diagnosed as AIS or 5α-RD according to clinical and hormonal evaluations were investigated. Sequence variants of
steroid 5-α-reductase type 2 were analyzed in cases with testosterone/dihydrotestosterone (T/DHT) ratio of ≥20, whereas the androgen
receptor (AR) gene was screened when the ratio was <20. Stepwise analysis of other associated genes were screened in cases with
no causative variant found in initial analysis. For statistical comparisons, the group was divided into three main groups and subgroups
according to their genetic diagnosis and T/DHT ratios.
Results: A total of 128 DSD patients from 125 non-related families were enrolled. Birth weight SDS and gestational weeks were significantly
higher in 5α-RD group than in AIS and undiagnosed groups. Completely female phenotype was higher in all subgroups of both AIS and
5α-RD patients than in the undiagnosed subgroups. In those patients with stimulated T/DHT <20 in the prepubertal period, stimulated
T/DHT ratio was significantly lower in AIS than in the undiagnosed group, and higher in 5α-RD. Phenotype associated variants were
detected in 24% (n=18 AIS, n=14 5α-RD) of the patients, revealing four novel AR variants (c.94G>T, p.Glu32*, c.330G>C, p.Leu110=;
c.2084C>T, p.Pro695Leu, c.2585_2592delAGCTCCTG, p.(Lys862Argfs*16), of these c.330G>C with silent status remained undefined in
terms of its causative effects.
Conclusion: T/DHT ratio is an important hormonal criterion, but in some cases, T/DHT ratio may lead to diagnostic confusion. Molecular
diagnosis is important for the robust diagnosis of 46,XY DSD patients. Four novel AR variants were identified in our study.
AU  - Darendeliler, Feyza
AU  - Poyrazoglu, Sukran
AU  - Toksoy, Güven
AU  - Altunoglu, Umut
AU  - Başaran, Seher
AU  - KARAMAN, VOLKAN
AU  - Avcı, Şahin
AU  - Karaman, Birsen
AU  - Aghayev, Agharza
AU  - Uyguner, Zehra Oya
AU  - Bundak, Ruveyde
AU  - Yavaş Abalı, Zehra
AU  - Bas, Firdevs
DO  - 10.4274/jcrpe.galenos.2022.2021-9-19
PY  - 2022
JO  - Journal of Clinical Research in Pediatric Endocrinology
VL  - 14
IS  - 2
SN  - 1308-5727
SP  - 153
EP  - 171
DB  - TRDizin
UR  - http://search/yayin/detay/530883
ER  -