CHARGE syndrome and related disorders: a mechanistic link.
Hum Mol Genet
; 30(23): 2215-2224, 2021 11 16.
Article
em En
| MEDLINE
| ID: mdl-34230955
ABSTRACT
CHARGE syndrome is an autosomal dominant malformation disorder caused by pathogenic variants in the chromatin remodeler CHD7. Affected are craniofacial structures, cranial nerves and multiple organ systems. Depending on the combination of malformations present, its distinction from other congenital disorders can be challenging. To gain a better insight into the regulatory disturbances in CHARGE syndrome, we performed RNA-Seq analysis on blood samples of 19 children with CHARGE syndrome and a confirmed disease-causing CHD7 variant in comparison with healthy control children. Our analysis revealed a distinct CHARGE syndrome pattern with downregulation of genes that are linked to disorders described to mimic the CHARGE phenotype, i.e. KMT2D and KDM6A (Kabuki syndrome), EP300 and CREBBP (Rubinstein-Taybi syndrome) and ARID1A and ARID1B (Coffin-Siris syndrome). Furthermore, by performing protein-protein interaction studies using co-immunoprecipitation, direct yeast-two hybrid and in situ proximity ligation assays, we could demonstrate an interplay between CHD7, KMT2D, KDM6A and EP300. In summary, our data demonstrate a mechanistic and regulatory link between the developmental disorders CHARGE-, Kabuki- and Rubinstein Taybi-syndrome providing an explanation for the overlapping phenotypes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Predisposição Genética para Doença
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Estudos de Associação Genética
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Síndrome CHARGE
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Doenças Genéticas Inatas
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article