A p.P30L Mutation at the CYP21A2 Gene in Macedonian Patients with Nonclassical Congenital Adrenal Hyperplasia

Abstract

Nonclassical congenital adrenal hyperplasia (NCAH) is an autosomal recessive imbalance in cortisol synthesis with adrenal androgen excess. Although rarely recognized in infants, it may cause premature adrenarche and pubarche, virilization in young women and variable symptoms in young men. It is commonly caused by mutations in CYP21A2, the gene for steroid 21-hydroxylase. Patients with the p.P30L allele tend to have pronounced evidence of androgen excess but are categorized as nonclassical. We used direct molecular detection of the p.P30L mutation in CYP21A2 in 11 Macedonian NCAH patients and in 17 members of their families using polymerase chain reaction/amplification created restriction site (PCR/ACRS) analysis and digestion with restriction enzymes. The p.P30L mutation was found in a homozygous state in seven (63.6%) and in a heterozygous state in four (36.4%) patients. Of the latter, one was also heterozygous for the p.Q318X mutation. The p.P30L mutation was found in a heterozygous state in 10 (58.8%) and in a homozygous state in one (5.9%) of the family members. These findings support a role of the p.P30L mutation in NCAH.

Testicular adrenal rest tumors in boys with 21-hydroxylase deficiency, timely diagnosis and follow-up

“…One of the patients was homozygous for p.P30L. This mutation is considered mild, however, when homozygous, can cause increased virilization similar to the SV form ( 25 , 26 , 27 ). We have not found a patient with TART and this genotype in the literature.…”

Pitfalls in molecular diagnosis of 21-hydroxylase deficiency in congenital adrenal hyperplasia

“…This problem severely limits the number of specific primers for CYP21A2 . [ 13 ] Most authors have used two fractions of CYP21A2 , which differ from CYP21P . One of them is 8-bp sequence in exon 3 of CYP21 and deleted in the pseudogene while another one in exon 6 has four different nucleotide between gene and pseudogene.…”