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- Title
A Novel Missense Mutation, GLY424SER, in Brazilian Patients with 21-Hydroxylase Deficiency.
- Authors
BILLERBECK, ANA ELISA C.; BACHEGA, TÂNIA A. S. S.; FRAZZATTO, ELIANA T.; MIRIAN YUMIE NISHI; GOLDBERG, ANNA CARLA; MARIN, MARIA LUCIA C.; MADUREIRA, GUIOMAR; MONTE, OSMAR; ARNHOLD, IVO J. P.; MENDONCA, BERENICE B.
- Abstract
A previous screening of 17 mutations in 130 Brazilian patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency did not identify mutations in 20% of the alleles. To diagnose these alleles we sequenced the entire CYP21 gene of one Mulatto patient with the simple virilizing form, who had only the R356W mutation in a heterozygous state. We identified a heterozygous G→A transition in codon 424. This mutation leads to a substitution of glycine by serine in a conserved region where glycine is conserved in at least 4 species. This novel mutation eliminates 1 of the restriction sites of the BanI enzyme, which made its screening possible for the whole series. The G424S mutation was found in a compound heterozygous state in 5 families; 4 presented the simple virilizing form, and 1 presented the nonclassical form. Interestingly, 3 of 5 families have a Mulatto origin. This mutation was not identified in 118 CYP21 alleles of normal individuals, ruling out the possibility of a polymorphism, or in 80 pseudogenes, indicating a casual mutagenic event and not a microconversion event. All patients with the G424S mutation presented CYP21P and C4A gene deletions and human leukocyte antigen DR17 on the same haplotype, suggesting a linkage disequilibrium and a probable founder effect. Search for the G424S mutation in other populations will reveal whether it is restricted to the Brazilian patients or if it has a wider ethnic distribution
- Publication
Journal of Clinical Endocrinology & Metabolism, 1999, Vol 84, Issue 8, p2870
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.84.8.2870