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.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase
/ deficiency
Adolescent
Adult
Child
Child, Preschool
Chromosome Aberrations
Dihydrotestosterone
/ blood
Disorders of Sex Development
/ complications
Female
Genetic Association Studies
Genital Neoplasms, Female
/ etiology
Genital Neoplasms, Male
/ etiology
Humans
Infant
Infant, Newborn
Male
Retrospective Studies
Risk Factors
Sex Factors
Sexual Maturation
Testosterone
/ blood
Turkey
Young Adult
Gender preference
Malignancy
Phenotype
SRD5A2 gene
Testosterone/dihydrotestosterone ratio
Journal
Journal of endocrinological investigation
ISSN: 1720-8386
Titre abrégé: J Endocrinol Invest
Pays: Italy
ID NLM: 7806594
Informations de publication
Date de publication:
Apr 2019
Apr 2019
Historique:
received:
07
04
2018
accepted:
06
08
2018
pubmed:
23
8
2018
medline:
28
7
2019
entrez:
23
8
2018
Statut:
ppublish
Résumé
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. 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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 30132287
doi: 10.1007/s40618-018-0940-y
pii: 10.1007/s40618-018-0940-y
doi:
Substances chimiques
Dihydrotestosterone
08J2K08A3Y
Testosterone
3XMK78S47O
3-Oxo-5-alpha-Steroid 4-Dehydrogenase
EC 1.3.99.5
steroid-5alpha-reductase type 2
EC 1.3.99.5
Types de publication
Journal Article
Multicenter Study
Langues
eng
Pagination
453-470Subventions
Organisme : Çocuk Endokrinolojisi ve Diyabet Derneği
ID : 032015
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