Background: Congenital adrenal hyperplasia (CAH) due to steroid 11β-hydroxylase deficiency is the second most common form of CAH, resulting from a mutation in the CYP11B1 gene. Steroid 11β-hydroxylase deficiency results in excessive mineralcorticoids and androgen production leading to hypertension, virilisation, and ambiguous genitalia of genetically female infants.
Objective: The aim of the study was to identify the molecular detect causing steroid 11β-hydroxylase deficiency in two patients from a Saudi family.
Methods: Two brothers aged 21- and 10-month-old presented with penile enlargement, progressive darkness of skin, hypertension, and cardiomyopathy. Their elder brother had the same family history and died at age of 30 months due to heart failure with severe dilated cardiomyopathy. All coding exons and intronexon boundary of CYP11B1 gene were amplified by PCR from peripheral leukocyte DNA of two patients and sequenced.
Results: A novel biallelic mutation in exon 4 of the CYP11B1 gene was found in both patients. The mutation c.780 G>A created a premature stop codon at amino acid 260 (p.W260*), resulting in a truncated protein devoid of 11β-hydroxylase activity. Interestingly, a somatic mutation at the same codon (c.779 G>A, p.W260*) was reported in a patient with papillary thyroid cancer (COSMIC database).Clinically, both patients were treated with hydrocortisone and anti-hypertensive medication. Nine months following treatment, cardiomyopathy disappeared with normal blood pressure and improvement in the skin pigmentation.
Conclusions: We have identified a novel nonsense mutation in the CYP11B1 gene that causes classic steroid 11β-hydroxylase deficient CAH. Cardiomyopathy and cardiac failure can be reversed by early diagnosis and treatment.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology