Mutations in the CYP21B gene in a Chilean population with simple virilizing congenital adrenal hyperplasia

Abstract

Steroid 21-hydroxylase deficiency (21OHD) compromises about 95% of all cases of congenital adrenal hyperplasia. We have characterized the disease-causing mutations in the steroid 21-hydroxylase genes of 19 Chilean patients (12 females and 7 males) with the simple virilizing (SV) form of 21OHD and compared them with other SV-populations. Using allele-specific polymerase chain reaction, we identified lesions in 28 chromosomes out of 38 tested (73.7%). The most frequent finding was the mutation I173N=12/38 (31.6%) similar as described in Caucasian, Asian and other Hispanic populations, where this mutation represents around 20-40% of the genetic defects in the CYP21B gene. The mutation V282L=4/38 (10.5%) and deletion (Del) or large gene conversion (LGC)=3/38 (7.9%) were also frequently detected. Only 2 alleles carried the mutation I2 splice (5.3%), this frequency is lower than that reported in Caucasian or in Mexican populations. We did not find alleles with the mutations R357W, Cluster E6, P31L and P454S in these patients. The complete genotype was determined in 11/19 patients (58%) and one allele in 6/19 patients (31.6%). In summary, about 30% of the Chilean population with SV 21OHD presented the missense mutation I173N as described in other populations. The frequency of the other lesions showed differences even between populations with similar genetic background.

Molecular CYP21A2 diagnosis in 480 Brazilian patients with congenital adrenal hyperplasia before newborn screening introduction

“…www.eje-online.org A strong positive genotype-phenotype association was verified, similar to that found in other ethnic groups (9,13,14,15,16,17,27,28,29,30,35). The saltwaster frequency was higher in the Null group than in group A, which is also important for clinical decisions in asymptomatic patients (18) during the neonatal period.…”

Neonatal 17‐hydroxyprogesterone levels adjusted according to age at sample collection and birthweight improve the efficacy of congenital adrenal hyperplasia newborn screening

“…33 However, the FPR rate related to the 99Á8th percentile seems more appropriate for our programme, in accordance with other studies. 17,23,34,35 Using the 99Á8th percentile as a cut-off adjusted to the two groups of sample collection times and to the four BW groups, we observed that there was significant improvement in the positive predictive value and in the specificity of a positive test with the fluoroimmunoassay, in agreement with other studies. 13,36 These cut-offs were efficient in identifying salt wasters, with a sensitivity of 100%.…”

“…Consequently, we established cut‐offs for each BW and sample collection time using the values of the 99·5th percentile, as suggested by the current NBS protocol of Sao Paulo state . However, the FPR rate related to the 99·8th percentile seems more appropriate for our programme, in accordance with other studies …”

Classical and nonclassical 21‐hydroxylase deficiency: a molecular study of Argentine patients

“…Ezquieta et al (1995); Italy: Carrera et al (1996); Balsamo et al (2000); Brazil: Bachega et al (1998). ‡Spain: Ezquieta et al (1995); Lobato et al (1999); Italy: Carrera et al (1996); Bobba et al (1999); Balsamo et al (2000); Argentina: Dardis et al (1997); Mexico: Ordoñez-Sánchez et al (1998); Brazil: Bachega et al (1998); Chile: Fardella et al (1998Fardella et al ( , 2000. Data for Mexico and Chile recalculated for classical alleles and SW + SV alleles, respectively.…”