Mutational Spectrum of the Steroid 21-Hydroxylase Gene in Austria: Identification of a Novel Missense Mutation

Abstract

This study attempted an analysis of the mutational spectrum of 21-hydroxylase deficiency in 79 unrelated Austrian patients with classical and nonclassical forms of congenital adrenal hyperplasia and their respective 112 family members. Apparent large gene deletions/conversions were present in 31% of the 158 unrelated congenital adrenal hyperplasia alleles, whereas the most frequent point mutations were intron 2 splice (22.8%), I172N (15.8%), V281L (12%), and P30L (7.6%), in line with the frequencies reported for other countries. In 5 of the 12 congenital adrenal hyperplasia alleles carrying a P30L mutation the aberration is based on a single base substitution, whereas the remaining 7 represent part of a CYP21B conversion (1 allele) or CYP21B/21A hybrid gene (6 alleles), the latter characterized by a junction site before

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

“…Despite the high miscegenation of our population, previous studies observed a high frequency of CAH in Brazil. 17,25,26 The present study demonstrates the importance of NBS implementation in Brazil, as it was effective in identifying the salt-wasting form, increasing the SW/SV proportion as well as normalizing the male/female ratio in comparison with data from the unscreened Brazilian cohort. 27 The data from Sao Paulo CAH-NBS are in accordance with those in the literature.…”

Substitutions in the CYP21A2 promoter explain the simple‐virilizing form of 21‐hydroxylase deficiency in patients harbouring a P30L mutation

“…Such cases demonstrate that the disease is a continuous spectrum of enzymatic deficiency and it is sometimes difficult to classify the patient into one of the three traditional categories. Regarding the 10 cases described by Baumgartner-Parzer et al 33 and Dolzan et al, 23 nine of them presented the simple virilizing form, while the remaining patient presented the nonclassical form with clitoromegaly ( Table 3). We suggest that the different phenotypes described by these authors in their patients bearing the pseudogene promoter and P30L mutation might depend on the presence of different mutations in the promoter region of the hybrid gene, although none of these studies has sequenced this promoter region.…”

“…In these cases, P30L belongs to a hybrid gene that encompasses the promoter region of the pseudogene in compound heterozygosis with a severe mutation. 23,[31][32][33] Based on these findings we studied two unrelated patients who presented the P30L mutation in compound heterozygosis with a severe mutation. However, the simple virilizing form observed in these patients was discordant from the moderate impairment of enzyme activity conferred by the genotype, suggesting the presence of additional mutations in the allele bearing the P30L mutation.…”

Frequency of RET Proto-Oncogene Mutations in Patients with Normal and with Moderately Elevated Pentagastrin-Stimulated Serum Concentrations of Calcitonin

“…Genomic DNA was extracted from peripheral blood leukocytes according to standard procedures (8). Five fragments covering the exons 10, 11, 13, 14, 15, and 16 of the RET proto-oncogene were specifically amplified by selective PCR primers (as shown in Table 1) designed by Drs.…”