Molecular genetics and phenotype/genotype correlation of 5-α reductase deficiency in a highly consanguineous population.

Autor: Alswailem, Meshael M., Alzahrani, Ohoud S., Alghofaili, Lamyaa, Qasem, Ebtesam, Almohanaa, Mai, Alsagheir, Afaf, Bin Abbas, Bassam, Attia, Najya A., Al Shaikh, Adnan, Alzahrani, Ali S.
Zdroj: Endocrine (1355008X); Feb2019, Vol. 63 Issue 2, p361-368, 8p
Abstrakt: Context and objectives: 5-α reductase deficiency is a rare 46,XY disorder of sex development. We present detailed phenotypic and genotypic features of a cohort of 24 subjects from a highly consanguineous population of Saudi ArabiaSubjects and Methods: We studied the clinical presentation and hormonal profiles of 24 subjects diagnosed with 5-α reductase deficiency and performed genetic testing on DNA isolated from their peripheral blood using polymerase chain reaction and direct sequencing of the SRD5A2.Results: All subjects had 46,XY karyotype and presented with atypical appearance of external genitalia ranging from clitoromegaly, micophallus with hypospadias, undescended testes to completely normally looking female genitalia. Thirteen (54%) of them had severe under virilization and were assigned female sex at birth. The other 11 subjects were raised as males. Stimulated Testosterone:Dihydrotestosterone ratio was high in all 16 subjects in whom it was measured. The genetic testing revealed 2 nonsense mutations (p.R103X and p.R227X) in 2 unrelated subjects, 3 missense mutations (p.P181L, p.A228T, p.R246Q) in 11 subjects and a splice site mutation (IVS1-2A > G) in 11 other subjects. There was significant phenotypic variability even in subjects with the same mutation and also within the same family.Conclusion: This is the first and largest report of the clinical and molecular genetics of 5-α reductase deficiency from the Middle East. It shows weak genotype/phenotype correlation and significant phenotypic heterogeneity. IVS1-2A > G mutation is the most common mutation and is likely to be a founder mutation in this part of the world. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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