Genotype–phenotype correlation, gonadal malignancy risk, gender preference, and testosterone/dihydrotestosterone ratio in steroid 5-alpha-reductase type 2 deficiency: a multicenter study from Turkey
Journal of Endocrinological Investigation, cilt.42, sa.4, ss.453-470, 2019 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 42 Sayı: 4
- Basım Tarihi: 2019
- Doi Numarası: 10.1007/s40618-018-0940-y
- Dergi Adı: Journal of Endocrinological Investigation
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.453-470
- Anahtar Kelimeler: SRD5A2 gene, Phenotype, Malignancy, Gender preference, Testosterone, dihydrotestosterone ratio
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Background: Studies regarding genetic and clinical characteristics, gender preference, and gonadal malignancy rates for steroid 5-alpha-reductase type 2 deficiency (5α-RD2) are limited and they were conducted on small number of patients. Objective: To present genotype–phenotype correlation, gonadal malignancy risk, gender preference, and diagnostic sensitivity of serum testosterone/dihydrotestosterone (T/DHT) ratio in patients with 5α-RD2. Materials and methods: Patients with variations in the SRD5A2 gene were included in the study. Demographic characteristics, phenotype, gender assignment, hormonal tests, molecular genetic data, and presence of gonadal malignancy were evaluated. Results: A total of 85 patients were included in the study. Abnormality of the external genitalia was the most dominant phenotype (92.9%). Gender assignment was male in 58.8% and female in 29.4% of the patients, while it was uncertain for 11.8%. Fourteen patients underwent bilateral gonadectomy, and no gonadal malignancy was detected. The most frequent pathogenic variants were p.Ala65Pro (30.6%), p.Leu55Gln (16.5%), and p.Gly196Ser (15.3%). The p.Ala65Pro and p.Leu55Gln showed more undervirilization than the p.Gly196Ser. The diagnostic sensitivity of stimulated T/DHT ratio was higher than baseline serum T/DHT ratio, even in pubertal patients. The cut-off values yielding the best sensitivity for stimulated T/DHT ratio were ≥ 8.5 for minipuberty, ≥ 10 for prepuberty, and ≥ 17 for puberty. Conclusion: There is no significant genotype–phenotype correlation in 5α-RD2. Gonadal malignancy risk seems to be low. If genetic analysis is not available at the time of diagnosis, stimulated T/DHT ratio can be useful, especially if different cut-off values are utilized in accordance with the pubertal status.