De novo variants in CNOT9 cause a neurodevelopmental disorder with or without epilepsy.
Genet Med
; 25(7): 100859, 2023 Jul.
Article
en En
| MEDLINE
| ID: mdl-37092538
ABSTRACT
PURPOSE:
The study aimed to clinically and molecularly characterize the neurodevelopmental disorder associated with heterozygous de novo variants in CNOT9.METHODS:
Individuals were clinically examined. Variants were identified using exome or genome sequencing. These variants were evaluated using in silico predictions, and their functional relevance was further assessed by molecular models and research in the literature. The variants have been classified according to the criteria of the American College of Medical Genetics.RESULTS:
We report on 7 individuals carrying de novo missense variants in CNOT9, p.(Arg46Gly), p.(Pro131Leu), and p.(Arg227His), and, recurrent in 4 unrelated individuals, p.(Arg292Trp). All affected persons have developmental delay/intellectual disability, with 5 of them showing seizures. Other symptoms include muscular hypotonia, facial dysmorphism, and behavioral abnormalities. Molecular modeling predicted that the variants are damaging and would lead to reduced protein stability or impaired recognition of interaction partners. Functional analyses in previous studies showed a pathogenic effect of p.(Pro131Leu) and p.(Arg227His).CONCLUSION:
We propose CNOT9 as a novel gene for neurodevelopmental disorder and epilepsy.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Epilepsia
/
Trastornos del Neurodesarrollo
/
Discapacidad Intelectual
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Genet Med
Asunto de la revista:
GENETICA MEDICA
Año:
2023
Tipo del documento:
Article