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.
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.