Donor splice mutation in the 11β-hydroxylase (CYP11B1) gene resulting in sex reversal: A case report and review of the literature

Background: Mutations in the gene encoding 11β-hydroxylase (CYP11B1) are the second most common cause of congenital adrenal hyperplasia (CAH), a disorder characterized by adrenal insufficiency and virilization of female external genitalia. Objective: We describe a new case of 11β-hydroxylase CAH caused by donor splice site mutation in the CYP11B1 gene. Patient: A 46,XX patient of Pakistani descent was identified with severe virilization soon after birth. The karyotype was negative for SRY. Pelvic ultrasound showed normal uterus and cervix. Periniogram revealed a 3-cm long urogenital sinus, ACTH stimulation test showed normal 17-hydroxyprogesterone, low cortisol, elevated 11-deoxycortisol and deoxycorticosterone (DOC) levels, consistent with 11β-hydroxylase deficiency. Glucocorticoid treatment was started on the basis of a low baseline cortisol and severely virilized external genitalia. The patient did not develop salt wasting and/or hypertension. Results: Analysis of the CYP11B1 gene revealed homozygosity for a codon 318+1G→C substitution at the 5′-splice donor site of intron 5 resulting in a missense mutation. The parents of the patients are consanguineous and are heterozygous for the same mutation. Conclusions: In a previous reported case a donor splice mutation was identified for the first time at the same position codon 318 of the CYP11B1 gene. We present this case in detail along with a literature review of 11β-hydroxylase deficiency CAH.