Genetic analysis of CHARGE syndrome identifies overlapping molecular biology.
Genet Med
; 20(9): 1022-1029, 2018 09.
Article
em En
| MEDLINE
| ID: mdl-29300383
ABSTRACT
PURPOSE:
CHARGE syndrome is an autosomal-dominant, multiple congenital anomaly condition characterized by vision and hearing loss, congenital heart disease, and malformations of craniofacial and other structures. Pathogenic variants in CHD7, encoding adenosine triphosphate-dependent chromodomain helicase DNA binding protein 7, are present in the majority of affected individuals. However, no causal variant can be found in 5-30% (depending on the cohort) of individuals with a clinical diagnosis of CHARGE syndrome.METHODS:
We performed whole-exome sequencing (WES) on 28 families from which at least one individual presented with features highly suggestive of CHARGE syndrome.RESULTS:
Pathogenic variants in CHD7 were present in 15 of 28 individuals (53.6%), whereas 4 (14.3%) individuals had pathogenic variants in other genes (RERE, KMT2D, EP300, or PUF60). A variant of uncertain clinical significance in KDM6A was identified in one (3.5%) individual. The remaining eight (28.6%) individuals were not found to have pathogenic variants by WES.CONCLUSION:
These results demonstrate that the phenotypic features of CHARGE syndrome overlap with multiple other rare single-gene syndromes. Additionally, they implicate a shared molecular pathology that disrupts epigenetic regulation of multiple-organ development.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA Helicases
/
Proteínas de Ligação a DNA
/
Síndrome CHARGE
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Child
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Child, preschool
/
Female
/
Humans
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Infant
/
Male
Idioma:
En
Revista:
Genet Med
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos