CYP21A2 mutations in pediatric patients with congenital adrenal hyperplasia in Costa Rica

Abstract

Steroid 21-hydroxylase deficiency accounts for 95% of congenital adrenal hyperplasia (CAH) cases. Newborn screening has allowed for early detection of the disease, and currently, molecular analysis can identify the genotypes of these patients. Phenotype-genotype correlation has been well described in previous studies. In Costa Rica, there is no data about the genetic background of these patients, nor their phenotypic correlation. Design Observational, retrospective, descriptive study based on the review of patient records who had a diagnosis of CAH and were performed molecular analysis using gene sequencing or MLPA during the period from 2006 to 2018 ( N = 58). Objective To describe the clinical and genetic characteristics of CAH patients due to 21-hydroxylase deficiency at the National Children's Hospital “Dr. Carlos Sáenz Herrera”, Caja Costarricense de Seguro Social (CCSS) in Costa Rica. Results 53% (31/58) of the patients were male and 80% (37/46) were born full term; 72% (42/58) had salt wasting phenotype, 9% (5/58) simple virilizing phenotype and 19% (11/58) non-classic phenotype. The most frequent variants were c.292+5G>A in 26% (15/58) of patients and Del/Del in 21% (12/58) of them. Conclusions The most frequent mutation in our study population was the c.292+5G>A, which was found in 15/58 patients. This rare variant has only been reported in three other studies so far but as an infrequent mutation in CAH patients. The genetic characteristics of Costa Rican patients differ from what has been documented worldwide and could respond to a founder effect.

Copy Number Variations in Genetic Diagnosis of Congenital Adrenal Hyperplasia Children

“…Using the MLPA technique, the prevalence of large deletions and large gene conversions in the present study was found in 29/112 (25.9%) patients with the SW phenotype. The results were in agreement with the work of Ben Charfeddine et al, 2012, who reported gene deletion/conversion in 11/50 Tunisian patients (22%) ( Kharrat et al, 2004 ; Ben Charfeddine et al, 2012 ; Chi et al, 2019 ; Umaña-Calderón et al, 2021 ).…”

Current Status of Newborn Bloodspot Screening Worldwide 2024: A Comprehensive Review of Recent Activities (2020–2023)

“…A recent evaluation of 3 years of screened newborns, CH referrals, and CH diagnoses confirmed the validity of the CH screening algorithm [ 1194 ]. The first mutation study of CAH patients from NBS identified an overabundance of cases with c.292 + 5G > A suggesting a possible founder effect [ 1195 ]. NBS expansion to include Wilson’s disease is also of interest because of the highest incidence globally (~1:20,000) [ 1196 ].…”

Characteristics of Congenital Adrenal Hyperplasia Diagnosed in Adulthood: A Literature Review and Case Series

“…However, a few patients with the I173N mutation and severe SW form have also been reported [ 20 , 21 , 22 ]. One of our female patients was homozygous for the c.293-13C>G mutation, which is mainly associated with the SW form [ 23 ]. Only a few cases of SV CAH with the c.293-13C>G mutation have been diagnosed, according to the literature [ 23 ].…”

“…One of our female patients was homozygous for the c.293-13C>G mutation, which is mainly associated with the SW form [ 23 ]. Only a few cases of SV CAH with the c.293-13C>G mutation have been diagnosed, according to the literature [ 23 ]. In two other patients, large deletions were found, compounded with severe mutations, c.293-13C>G/deletion, and I173N/deletion.…”

“…In two other patients, large deletions were found, compounded with severe mutations, c.293-13C>G/deletion, and I173N/deletion. Surprisingly, a large analysis of families affected by CAH has shown that c.293-13C>G/deletion was mainly associated with SW forms, while I173N/deletion was associated with SV CAH [ 23 ]. In European populations, the frequency of I173N mutations ranged from 12.4 to 19.7%, and that of c.293-13C>G ranged from 26.6 to 30.3%.…”