Phenotype and genotype correlation of the microconversion from the CYP21A1P to the CYP21A2 gene in congenital adrenal hyperplasia
Braz. j. med. biol. res
;
36(10): 1311-1318, Oct. 2003. tab
Article
in English
| LILACS
| ID: lil-346486
ABSTRACT
Deficiency of 21-hydroxylase is the most common form of congenital adrenal hyperplasia (CAH-21OH). We determined by allele-specific PCR the frequency of microconversion in the CYP21A2 gene in 50 Brazilian patients with the classical (salt wasting SW and simple virilizing SV) forms and nonclassical (NC) form of CAH-21OH and correlated genotype with phenotype. Genotypes were classified into three mutation groups (A, B, and C) based on the amount of enzymatic activity in in vitro studies using adrenal cells. In 94 unrelated alleles, we diagnosed 76 percent of the affected alleles after screening for 7 microconversions. The most frequent point mutations observed in this series were I172N (19 percent), V281L (18 percent), and IVS2,A/C>G,-12 (15 percent). In the SW form, the most frequent mutation was IVS2,A/C>G,-12 (38 percent), in the SV form it was I172N (53 percent), and in the NC form it was V281L (57.7 percent). We observed a good correlation between genotype and phenotype. Discordance between genotype and phenotype was found in one SV patient with a mild mutation in one of the alleles (R356W/V281L). However, we cannot rule out the presence of an additional mutation in these alleles. We also observed a good correlation of genotype with 17alpha-hydroxyprogesterone, testosterone, and androstenedione levels. The severity of external genitalia virilization correlated with the severity of mutation. In conclusion, the frequencies described in the present study did not differ from worldwide studies, including the Brazilian population. The few differences observed may reflect individual sample variations. This new Brazilian cohort study suggests the presence of new mutations in Brazilian patients with different forms of CAH-21OH
Full text:
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Index:
LILACS (Americas)
Main subject:
Point Mutation
/
Adrenal Hyperplasia, Congenital
/
Gene Conversion
Type of study:
Etiology study
/
Incidence study
/
Observational study
/
Risk factors
Limits:
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Language:
English
Journal:
Braz. j. med. biol. res
Journal subject:
Biology
/
Medicine
Year:
2003
Type:
Article
/
Project document
Affiliation country:
Brazil
Institution/Affiliation country:
Universidade Estadual de Campinas/BR
/
Universidade de Säo Paulo/BR
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