ClinVar

Hiort et al. (2005) reported a 46,XY patient with a homozygous defect of CYP11A1. This child was born prematurely with sex reversal and severe adrenal insufficiency (613743). Laboratory data showed diminished or absent steroidogenesis in all pathways. Molecular genetic analysis of the CYP11A1 gene revealed a homozygous single-nucleotide deletion of adenine at position 835 in exon 5, leading to a premature termination at codon 288. This mutation was predicted to delete highly conserved regions of the P450scc enzyme and thus to lead to a nonfunctional protein. Both healthy parents were heterozygous for this mutation. Hiort et al. (2005) stated that this was the first report of an inherited disruptive mutation in the CYP11A1 gene.

Kim et al. (2008) described a patient with 46,XY sex reversal and primary adrenal failure who was compound heterozygous for the 835delA mutation and a splice site mutation (IVS3+(2-3)insT; 118485.0006). External genitalia were those of a normal female; no gonads, internal reproductive structures, or adrenals were identified by MRI or ultrasound, and a genitogram revealed a blind vaginal pouch. Functional studies in COS-1 cells demonstrated no activity of 835delA-mutated P450scc. The IVS3+(2-3)insT mutation introduces an additional thymidine after the second base of the third intron that was predicted to disrupt the splice donor site. PCR amplification of RNA demonstrated that sequences corresponding to intron 3 had been retained, resulting in a nonfunctional protein.

Sahakitrungruang et al. (2010) identified the 835delA mutation in 2 sibs with adrenal insufficiency. The 46,XY sib had micropenis, severe hypospadias, bifid scrotum, and cryptorchidism; the other sib was 46,XX with normal female genitalia. The sibs carried the 835delA mutation in compound heterozygosity with a missense mutation.