TY - JOUR
T1 - Translational pediatrics
T2 - clinical perspective for Phelan–McDermid syndrome and autism research
AU - Sakai, Yasunari
AU - Kawaguchi, Sayaka
AU - Schaaf, Christian P.
AU - Ohga, Shouichi
N1 - Funding Information:
This study was supported by JSPS KAKENHI grant numbers JP19K08281, JP18H04042, JP21K10293; AMED under the grant numbers JP20ek0109411 and JP20wm0325002h; a Health and Labour Sciences Research Grant for Prion Diseases under the grant number JP20FC1054; The Japan Epilepsy Research Foundation, and Kawano Masanori Memorial Public Interest Incorporated Foundation for Promotion of Pediatrics. These funders had no role in the design and conduct of the study.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
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U2 - 10.1038/s41390-021-01806-x
DO - 10.1038/s41390-021-01806-x
M3 - Review article
C2 - 34702975
AN - SCOPUS:85118149750
JO - Pediatric Research
JF - Pediatric Research
SN - 0031-3998
ER -