Background: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder in which more than 90% of CAH cases are caused by mutations of the 21-hydroxylase (CYP21A2) gene.
Objective and hypotheses: To determine the mutational spectrum in Egyptian CAH patients attending Diabetes Endocrine and Metabolism Pediatric Unit (DEMPU) including family members of CAH patients.
Method: The use of reverse hybridization assay for the molecular diagnosis of common mutations in CYP21A2 gene in Egyptian patients with 21-OH deficiency CAH.
Results: 98 CAH cases, diagnosed based on the clinical phenotype and elevated 17 OHP, along with 15 controls were tested by strip hybridization assay, 16 of them were further confirmed by real time PCR. Patients were 70 females and 28 males, with ages 6.2±5.3 and 4.3±4.9 years, respectively. 76 cases presented with salt wasting, 19 presented with simple virilizing form, late onset CAH was seen in only three cases. The most common mutations encountered were homozygous mutations for I2 splice, accounting for 14.2% of the analyzed cases. The most common combination seen is the combined homozygousity of three mutations namely the p.P30L, I2 splice and the 8 bp deletion present in 12% of the cases. The third most frequent genotype interestingly, was the normal genotype (negative to all listed mutations) accounting for 11% of cases; meanwhile these cases expressed the typical phenotype of the disease, therefore mutations in these patients will be detected by another method (DNA sequencing) and if still found normal by DNA sequencing they will screened for other enzyme deficiencies causing CAH (3β-hydroxysteroid dehydrogenase and 11β-hydroxylase deficiencies). Furthermore, 5% of the cases showed a single heterozygous mutation, which is not sufficient to explain the observed phenotypes either.
Conclusion: Strip hybridisation assay is an easy, rapid and cost effective testing for CAH patients and their families.
Funding: This work was supported by the STDF; project ID (4671).
01 - 03 Oct 2015
European Society for Paediatric Endocrinology