Bi-allelic variants in CHKA cause a neurodevelopmental disorder with epilepsy and microcephaly.
Brain
; 145(6): 1916-1923, 2022 06 30.
Article
en En
| MEDLINE
| ID: mdl-35202461
ABSTRACT
The Kennedy pathways catalyse the de novo synthesis of phosphatidylcholine and phosphatidylethanolamine, the most abundant components of eukaryotic cell membranes. In recent years, these pathways have moved into clinical focus because four of ten genes involved have been associated with a range of autosomal recessive rare diseases such as a neurodevelopmental disorder with muscular dystrophy (CHKB), bone abnormalities and cone-rod dystrophy (PCYT1A) and spastic paraplegia (PCYT2, SELENOI). We identified six individuals from five families with bi-allelic variants in CHKA presenting with severe global developmental delay, epilepsy, movement disorders and microcephaly. Using structural molecular modelling and functional testing of the variants in a cell-based Saccharomyces cerevisiae model, we determined that these variants reduce the enzymatic activity of CHKA and confer a significant impairment of the first enzymatic step of the Kennedy pathway. In summary, we present CHKA as a novel autosomal recessive gene for a neurodevelopmental disorder with epilepsy and microcephaly.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Colina Quinasa
/
Epilepsia
/
Trastornos del Neurodesarrollo
/
Microcefalia
/
Malformaciones del Sistema Nervioso
Límite:
Humans
Idioma:
En
Revista:
Brain
Año:
2022
Tipo del documento:
Article
País de afiliación:
Alemania