A Abacı1, G Çatlı2, Ö Kırbıyık3, N M Şahin4, Z Y Abalı5, E Ünal6, Z Şıklar7, E Mengen8, S Özen9, T Güran10, C Kara11, M Yıldız12, E Eren13, Ö Nalbantoğlu14, A Güven15,16, A Çayır17, E D Akbaş18, Y Kor19, Y Çürek20, Z Aycan4, F Baş5, Ş Darcan9, M Berberoğlu7. 1. Department of Pediatric Endocrinology, Faculty of Medicine, Dokuz Eylül University, Balcova, 35340, Izmir, Turkey. ayhanabaci@gmail.com. 2. Department of Pediatric Endocrinology, Faculty of Medicine, İzmir Katip Çelebi University, Izmir, Turkey. 3. Division of Genetics, Tepecik Training and Research Hospital, Sağlık Bilimleri University, Izmir, Turkey. 4. Department of Pediatric Endocrinology, Faculty of Medicine and Dr Sami Ulus Woman Health and Children Research Hospital, Yıldırım Beyazıt University, Ankara, Turkey. 5. Department of Pediatric Endocrinology, Faculty of Medicine, İstanbul University, İstanbul, Turkey. 6. Department of Pediatric Endocrinology, Faculty of Medicine, Dicle University, Diyarbakır, Turkey. 7. Department of Pediatric Endocrinology, Faculty of Medicine, Ankara University, Ankara, Turkey. 8. Department of Pediatric Endocrinology, Faculty of Medicine, Çukurova University, Adana, Turkey. 9. Department of Pediatric Endocrinology, Faculty of Medicine, Ege University, Izmir, Turkey. 10. Department of Pediatric Endocrinology, Faculty of Medicine, Marmara University, İstanbul, Turkey. 11. Department of Pediatric Endocrinology, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey. 12. Division of Pediatric Endocrinology, Kanuni Sultan Süleyman Training and Research Hospital, İstanbul, Turkey. 13. Department of Pediatric Endocrinology, Faculty of Medicine, Uludağ University, Bursa, Turkey. 14. Division of Pediatric Endocrinology, Dr. Behcet Uz Children's Hospital, Izmir, Turkey. 15. Department of Pediatric Endocrinology, Göztepe Training and Research Hospital, İstanbul, Turkey. 16. Department of Pediatric Endocrinology, Faculty of Medicine, Amasya University, Amasya, Turkey. 17. Division of Pediatric Endocrinology, Erzurum Training and Research Hospital, Erzurum, Turkey. 18. Department of Pediatric Endocrinology, Faculty of Medicine, Gazi University, Ankara, Turkey. 19. Department of Pediatric Endocrinology, Numune Training and Research Hospital, Sağlık Bilimleri University, Adana, Turkey. 20. Department of Pediatric Endocrinology, Sağlık Bilimleri University Antalya Training and Research Hospital, Antalya, Turkey.
Abstract
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.
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.
Entities:
Keywords:
Gender preference; Malignancy; Phenotype; SRD5A2 gene; Testosterone/dihydrotestosterone ratio
Authors: Yolande van Bever; Hennie T Brüggenwirth; Katja P Wolffenbuttel; Arianne B Dessens; Irene A L Groenenberg; Maarten F C M Knapen; Elfride De Baere; Martine Cools; Conny M A van Ravenswaaij-Arts; Birgit Sikkema-Raddatz; Hedi Claahsen-van der Grinten; Marlies Kempers; Tuula Rinne; Remko Hersmus; Leendert Looijenga; Sabine E Hannema Journal: J Med Genet Date: 2020-04-17 Impact factor: 6.318