Abstract
During the prenatal period, steroidogenic factor 1 is required for the development of the adrenal glands and for gonadal determination and differentiation, and after birth, it regulates gonadal progenitor cell formation and their survival. Here, we describe the clinical phenotype of three 46,XY patients (2 brothers and an unrelated subject) with disorder of sex development due to the same genetic variant. All patients underwent hormonal and pelvic ultrasound studies. Sequence analysis and deletion/duplication testing of a panel encompassing 8 genes (AR, DHH, MAP3K1, NROB1, SRD5A2, SRY, WT1, and nuclear receptor subfamily 5, group A, member 1 [NR5A1]) were performed in the index cases. All family members were tested for the presence of the NR5A1 variant. A variant previously described as likely pathogenic in NR5A1 (c.251G>A, p.Arg84His) that segregated in 1 family with different degrees of under-virilization was found. The family 1 index case (IV2) and his brother (IV3) had an external masculinization scale score of 5/12, but only the index case had Müllerian remnants; however, the family 2 patient had a milder score of 9/12. The older female relatives of family 1 who harbor this variant experienced premature menopause. To our k...Continue Reading
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