Genotype-phenotype correlation in 1,507 families with congenital adrenal hyperplasia owing to 21-hydroxylase deficiency.
Proc Natl Acad Sci U S A
; 110(7): 2611-6, 2013 Feb 12.
Article
em En
| MEDLINE
| ID: mdl-23359698
ABSTRACT
Over the last two decades, we have extensively studied the genetics of congenital adrenal hyperplasia caused by 21-hydroxylase deficiency (CAH) and have performed 8,290 DNA analyses of the CYP21A2 gene on members of 4,857 families at risk for CAH--the largest cohort of CAH patients reported to date. Of the families studied, 1,507 had at least one member affected with one of three known forms of CAH, namely salt wasting, simple virilizing, or nonclassical CAH. Here, we report the genotype and phenotype of each affected patient, as well as the ethnic group and country of origin for each patient. We showed that 21 of 45 genotypes yielded a phenotypic correlation in our patient cohort. In particular, contrary to what is generally reported in the literature, we found that certain mutations, for example, the P30L, I2G, and I172N mutations, yielded different CAH phenotypes. In salt wasting and nonclassical CAH, a phenotype can be attributed to a genotype; however, in simple virilizing CAH, we observe wide phenotypic variability, particularly with the exon 4 I172N mutation. Finally, there was a high frequency of homozygous I2G and V281L mutations in Middle Eastern and Ashkenazi Jewish populations, respectively. By identifying the predominant phenotype for a given genotype, these findings should assist physicians in prenatal diagnosis and genetic counseling of parents who are at risk for having a child with CAH.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fenótipo
/
Esteroide 21-Hidroxilase
/
Hiperplasia Suprarrenal Congênita
Tipo de estudo:
Etiology_studies
/
Incidence_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
País/Região como assunto:
America do norte
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos