A novel homozygous disruptive mutation in the SRD5A2-gene in a partially virilized patient with 5α-reductase deficiency

Steroid 5α-reductase deficiency is a rare autosomal recessive disorder caused by mutations in the SRD5A2-gene, resulting in diminished dihydrotestosterone (DHT) formation and, hence, in a severe virilization deficit of the external genitalia in patients with 46,XY karyotype. The phenotype of affected individuals is variable and has been reported to range from completely female over genital ambiguity to normal male, depending on the type of mutation and its effect on enzyme activity. Here we report an adolescent 46,XY patient with predominantly female appearance, who had been gonadectomized in early infancy. Genital status revealed a urogenital sinus equivalent to Prader stage III. Molecular genetic analysis demonstrated a homozygous point mutation in exon 2 of the SRD5A2-gene, leading to a premature termination in codon position 111 of the 5α-reductase 2 enzyme, and not allowing formation of a functional 5α-reductase type 2 enzyme. This case demonstrates that even despite a complete loss of function of 5αa-reductase type 2, marked virilization is possible, most likely the result of a testosterone (T) effect during foetal life.