Donor splice mutation in the 11beta-hydroxylase (CypllB1) gene resulting in sex reversal: a case report and review of the literature.
BACKGROUND
Mutations in the gene encoding 110-hydroxylase (CYPI]BJ) 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 1113-hydroxylase CAH caused by donor splice site mutation in the CYPllB1 gene.


METHODS
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 11beta-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 CYPllBlgene 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 CYPIIB1 gene. We present this case in detail along with a literature review of 11beta-hydroxylase deficiency CAH.
Bhangoo
Amrit
A
Pediatric Endocrinology Division of Infants and Children's Hospital of Brooklyn at Maimonides, Brooklyn, NY, USA.
Wilson
Robert
R
New
Maria I
MI
Ten
Svetlana
S
D000312:Adrenal Hyperplasia, Congenital / Q000201:enzymology* / Q000235:genetics* / Q000601:surgery; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics*
D004247:DNA; D013252:Steroid 11-beta-Hydroxylase