A Novel Mutation in the CYP11B1 Gene Causes Steroid 11ß-Hydroxylase Deficient Congenital Adrenal Hyperplasia with Reversible Cardiomyopathy.

Congenital adrenal hyperplasia (CAH) due to steroid 11ß-hydroxylase deficiency is the second most common form of CAH, resulting from a mutation in the CYP11B1 gene. Steroid 11ß-hydroxylase deficiency results in excessive mineralcorticoids and androgen production leading to hypertension, precocious puberty with acne, enlarged penis, and hyperpigmentation of scrotum of genetically male infants. In the present study, we reported 3 male cases from a Saudi family who presented with penile enlargement, progressive darkness of skin, hypertension, and cardiomyopathy. The elder patient died due to heart failure and his younger brothers were treated with hydrocortisone and antihypertensive medications. Six months following treatment, cardiomyopathy disappeared with normal blood pressure and improvement in the skin pigmentation. The underlying molecular defect was investigated by PCR-sequencing analysis of all coding exons and intron-exon boundary of the CYP11B1 gene. A novel biallelic mutation c.780 G>A in exon 4 of the CYP11B1 gene was found in the patients. The mutation created a premature stop codon at amino acid 260 (p.W260 (∗) ), resulting in a truncated protein devoid of 11ß-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). In conclusion, we have identified a novel nonsense mutation in the CYP11B1 gene that causes classic steroid 11ß-hydroxylase deficient CAH. Cardiomyopathy and cardiac failure can be reversed by early diagnosis and treatment.

Corneal decompensation in recessive cornea plana.

PURPOSE: To report corneal decompensation in 3 patients with recessive cornea plana. METHODS: Retrospective case series. RESULTS: An adult and two children (all unrelated) with clinical recessive cornea plana had gradual decrease in vision. Ophthalmic examination revealed corneal decompensation (stromal thickening and haze without epithelial changes) in the 3 patients. Diagnostic DNA sequencing revealed homozygosity for a novel splice (c.995-2A>G) in the adult and 2 previously reported KERA mutations in the 2 children (c.1033delC[p.C343AFsX] and c.945C > T[p.R313X]). CONCLUSIONS: The phenotype of recessive cornea plana can rarely include corneal decompensation. There are likely modifying factors that can lead to endothelial cell dysfunction in the setting of homozygous KERA mutation.