Molecular characterization of CYP21A2 mutations and clinical findings in Macedonian patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency – twenty years experience
Year: 2024
Type: book-chapter
Study design: Observational Study
Abstract: Congenital adrenal hyperplasia (CAH) is a heterogeneous autosomal recessive disease which has a different prevalence in different populations and ethnicities. The disease is caused by a variety of CYP21A2 gene mutations. The most common mutations affect the enzyme 21-hydroxylase. CAH has variable clinical presentation depending on the amount of the active enzyme. Where no enzyme is produced, the lifethreatening disease occurs in newborn child, whereas milder mutations can produce some percentage of 21-hyroxylase causing milder clinical presentation with precocious puberty in childhood, or oligomenorrhea and sterility later in life. In female, additional signs are virilization which can be present as complete sexual ambiguity and problems with sexual identity which can occur despite the surgical correction. In this paper we have presented the 20 years of work with clinical and molecular issues in 96 Macedonian CAH patients with all forms of severity. The diagnosis and clinical care were provided following the contemporary international guidelines. Nine most common CYP21A2 point mutations were explored and the findings are classified through the severity of mutations and their role in the clinical presentation. The mutations distribution in our population corresponds to most of the European countries with exception of the p.P30L mutation which has higher prevalence. Genotype-phenotype concordance was good in our cohort except for a stronger role of p.P30L mutation which delivered stronger virilization in NC form or even complete SV form of the disease. We have presented a novel 9 bp deletion (p.G424_R426del) in exon 10 of the CYP21A2 gene. We have provided our finding that some mutations such as p.P30L and intron 2 are among the main causes of genotype-phenotype discrepancy. We had presented also several rare genotypes and the genotypes in Roma ethnicity for the first time. We believe that genetic testing in patients with CAH is important for the exact diagnosis, understanding the role of mutations and for genetic counseling.
Authors: Anastasovska, Violeta, Kocova, Mirjana
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7020827582