Translational pediatrics: clinical perspective for Phelan-McDermid syndrome and autism research.
Pediatr Res
; 92(2): 373-377, 2022 08.
Article
em En
| MEDLINE
| ID: mdl-34702975
ABSTRACT
Phelan-McDermid syndrome (PMS) is a rare genetic disorder presenting with developmental delay, epilepsy, and autism spectrum disorder (ASD). The segmental deletion of chromosome 22q13.3 affects the copy number of SHANK3, the gene encoding a scaffolding protein at the postsynaptic density. Biological studies indicate that SHANK3 plays crucial roles in the development of synaptic functions in the postnatal brain. Notably, induced pluripotent stem (iPS) cells have enabled researchers to develop brain organoids and microglia from patients and to explore the pathophysiology of neurodevelopmental disorders in human cells. Single-cell RNA sequencing of these cells revealed that human-specific genes are uniquely expressed during cortical development. Thus, patient-derived disease models are expected to identify as-yet-unidentified functions of SHANK3 in the development of human brain. These efforts may help establish a new style of translational research in pediatrics, which is expected to provide therapeutic insight for children with PMS and broader categories of disease. IMPACT Phelan-McDermid syndrome is a prototypic model for molecular studies of autism spectrum disorder. Brain organoids are expected to provide therapeutic insight. Single-cell RNA sequencing of microglia may uncover the functional roles of human-specific genes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pediatria
/
Transtorno Autístico
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Transtorno do Espectro Autista
Limite:
Child
/
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article