1. Inicio
  2. Publicaciones
  3. Muscarinic acetylcholine receptor M1 mutations causing neurodevelopmental disorder and epilepsy.

Muscarinic acetylcholine receptor M1 mutations causing neurodevelopmental disorder and epilepsy.

Fecha de publicación: Fecha Ahead of Print:

Autores de I3PT

Participantes ajenos a I3PT

  • Marcé-Grau A
  • Elorza-Vidal X
  • Pérez-Rius C
  • Sala-Coromina J
  • Estévez R
  • Macaya A

Grupos de Investigación

Abstract

De novo rare damaging variants in genes involved in critical developmental pathways, notably regulation of synaptic transmission, have emerged as a frequent cause of neurodevelopmental disorders (NDD). NDD show great locus heterogeneity and for many of the associated genes, there is substantial phenotypic diversity, including epilepsy, intellectual disability, autism spectrum disorder, movement disorders, and combinations thereof. We report two unrelated patients, a young girl with early-onset refractory epilepsy, severe disability, and progressive cerebral and cerebellar atrophy, and a second girl with mild dysmorphism, global developmental delay, and moderate intellectual disability in whom trio-based whole-exome sequencing analysis uncovered de novo missense variants in CHRM1. Biochemical analyses of one of the NDD-associated variants proved that it caused a reduction in protein levels and impaired cellular trafficking. In addition, the mutated receptor showed defective activation of intracellular signaling pathways. Our data strengthen the concept that brain-reduced muscarinic signaling lowers the seizure threshold and severely impairs neurodevelopment.

Datos de la publicación

ISSN/ISSNe:
1059-7794, 1098-1004

HUMAN MUTATION  WILEY

Tipo:
Article
Páginas:
1215-1220
PubMed:
34212451

Citas Recibidas en Web of Science: 4

Documentos

  • No hay documentos

Métricas

Filiaciones mostrar / ocultar

Keywords

  • epileptic encephalopathy, muscarinic receptor, whole-exome sequencing

Campos de Estudio

Compartir