You are here Patient Care Genetics Laboratory Research Congenital Adrenal Hyperplasia

Congenital Adrenal Hyperplasia

Prevalence of Congenital Adrenal hyperplasia (CAH), due to 21-hydroxylase deficiency, in a Jordanian sample pool

CAH represents a family of autosomal recessive disorders.  About 95% of the CAH cases are caused by 21-hydroxylase deficiency, resulting from a defect in the CYP21A2 gene. The main aim of the current study was to screen the Jordanian population for the 8 most common small CYP21A2 mutations and introduce a prenatal and a neonatal genetic test for CAH in Jordan. Similar mutational analysis studies have been performed in other Arab countries such as Tunisia, and Lebanon, however, this is a first comprehensive study of its kind, performed on the Jordanian population. Although no accurate population study exist, it is very clear that the incidence of CAH in Jordan is high (based on the high percentage of consanguineous marriages and high number of CAH patients being admitted to clinics nationwide).  Current sample study consisted of 71 clinically diagnosed index patients, including 40 males and 25 females. In most cases, DNA samples for family members were also available, bringing the total number of samples up to 200. As a screening method we implemented the amplification refractory mutation system (ARMS), optimizing conditions for the 8 most common CYP21A2 mutations ( P30L in exon1, In2cs in intron 2, 8bp deletion in exon 3, I172N in exon 4, exon 6 cluster mutation, V281L in exon 7, Q318X and R356W in exon 8). Mutation frequency was the highest for In2cs mutation, followed by Q318X and 8bp deletion. Although this mutational spread was unique to the Jordanian population, the prevalence of the In2cs mutation was in agreement with the average world studies conducted in 2003 (Kotaska K, Lisa L, Prusa R. Common CYP21 gene mutations in Czech patients and statistical analysis of worldwide mutation distribution. Cent Eur J Public Health; 11: 124-128). It is important to also note that in 25% of CAH cases due to CYP21A2 gene defect, mutations are caused by large gene deletions (i.e. 30 kb gene deletion). Furthermore, based on the average world studies, large deletions are the second most prevalent form of CYP21A2 defect in the general population. Hence, to be able to obtain a true statistical representation of CYP21A2 mutations in the Jordanian population, our sample pool needs to be tested for the 30 kb deletion. This will be achieved through Multiple Ligation-dependant Probe Amplification (MLPA) method, utilizing a CAH-MLPA kit. Once the mutational analysis is complete, we can implement a prenatal and a neonatal testing on a national scale, hoping to reduce the overall incidence of CAH in a Jordanian population.