PMID- 33226471
OWN - NLM
STAT- MEDLINE
DCOM- 20211025
LR  - 20240330
IS  - 1432-0533 (Electronic)
IS  - 0001-6322 (Print)
IS  - 0001-6322 (Linking)
VI  - 141
IP  - 2
DP  - 2021 Feb
TI  - Intellectual disability: dendritic anomalies and emerging genetic perspectives.
PG  - 139-158
LID - 10.1007/s00401-020-02244-5 [doi]
AB  - Intellectual disability (ID) corresponds to several neurodevelopmental disorders 
      of heterogeneous origin in which cognitive deficits are commonly associated with 
      abnormalities of dendrites and dendritic spines. These histological changes in 
      the brain serve as a proxy for underlying deficits in neuronal network 
      connectivity, mostly a result of genetic factors. Historically, chromosomal 
      abnormalities have been reported by conventional karyotyping, targeted 
      fluorescence in situ hybridization (FISH), and chromosomal microarray analysis. 
      More recently, cytogenomic mapping, whole-exome sequencing, and bioinformatic 
      mining have led to the identification of novel candidate genes, including genes 
      involved in neuritogenesis, dendrite maintenance, and synaptic plasticity. 
      Greater understanding of the roles of these putative ID genes and their 
      functional interactions might boost investigations into determining the plausible 
      link between cellular and behavioral alterations as well as the mechanisms 
      contributing to the cognitive impairment observed in ID. Genetic data combined 
      with histological abnormalities, clinical presentation, and transgenic animal 
      models provide support for the primacy of dysregulation in dendrite structure and 
      function as the basis for the cognitive deficits observed in ID. In this review, 
      we highlight the importance of dendrite pathophysiology in the etiologies of four 
      prototypical ID syndromes, namely Down Syndrome (DS), Rett Syndrome (RTT), 
      Digeorge Syndrome (DGS) and Fragile X Syndrome (FXS). Clinical characteristics of 
      ID have also been reported in individuals with deletions in the long arm of 
      chromosome 10 (the q26.2/q26.3), a region containing the gene for the collapsin 
      response mediator protein 3 (CRMP3), also known as dihydropyrimidinase-related 
      protein-4 (DRP-4, DPYSL4), which is involved in dendritogenesis. Following a 
      discussion of clinical and genetic findings in these syndromes and their 
      preclinical animal models, we lionize CRMP3/DPYSL4 as a novel candidate gene for 
      ID that may be ripe for therapeutic intervention.
FAU - Quach, Tam T
AU  - Quach TT
AD  - Institute for Behavioral Medicine Research, Wexner Medical Center, The Ohio State 
      University, Columbus, OH, 43210, USA.
AD  - INSERM U1217/CNRS, UMR5310, Universite de Lyon, Universite Claude Bernard Lyon 1, 
      Lyon, France.
FAU - Stratton, Harrison J
AU  - Stratton HJ
AD  - Department of Pharmacology, University of Arizona, Tucson, AZ, 85724, USA.
FAU - Khanna, Rajesh
AU  - Khanna R
AD  - Department of Pharmacology, University of Arizona, Tucson, AZ, 85724, USA.
FAU - Kolattukudy, Pappachan E
AU  - Kolattukudy PE
AD  - Department of Biological Chemistry and Pharmacology, Columbus, OH, 43210, USA.
FAU - Honnorat, Jerome
AU  - Honnorat J
AD  - INSERM U1217/CNRS, UMR5310, Universite de Lyon, Universite Claude Bernard Lyon 1, 
      Lyon, France.
AD  - French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune 
      Encephalitis, Hospices Civils de Lyon, Lyon, France.
AD  - SynatAc Team, Institut NeuroMyoGene, Lyon, France.
FAU - Meyer, Kathrin
AU  - Meyer K
AD  - The Research Institute of Nationwide Children Hospital, Columbus, OH, 43205, USA.
AD  - Department of Pediatric, The Ohio State University, Columbus, OH, 43210, USA.
FAU - Duchemin, Anne-Marie
AU  - Duchemin AM
AUID- ORCID: 0000-0003-3655-1747
AD  - Department of Psychiatry and Behavioral Health, The Ohio State University, 
      Columbus, OH, 43210, USA. Anne-Marie.Duchemin@osumc.edu.
LA  - eng
GR  - R01 DA042852/DA/NIDA NIH HHS/United States
GR  - R01 NS098772/NS/NINDS NIH HHS/United States
GR  - R01DA04285202/NH/NIH HHS/United States
GR  - R01NS09877202/NH/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20201123
PL  - Germany
TA  - Acta Neuropathol
JT  - Acta neuropathologica
JID - 0412041
RN  - 0 (DPYSL4 protein, human)
RN  - 0 (Nerve Tissue Proteins)
SB  - IM
MH  - Animals
MH  - Child, Preschool
MH  - Chromosome Aberrations
MH  - Dendrites/*genetics/*pathology
MH  - Humans
MH  - Intellectual Disability/*genetics/*pathology
MH  - Nerve Tissue Proteins/genetics
PMC - PMC7855540
MID - NIHMS1649330
OTO - NOTNLM
OT  - CRMP3/DPYSL4
OT  - Chromosome 10 (q26) deletion
OT  - Dendrite dysgenesis
OT  - Intellectual disability
OT  - Transgenic mice
EDAT- 2020/11/24 06:00
MHDA- 2021/10/26 06:00
PMCR- 2022/02/01
CRDT- 2020/11/23 12:10
PHST- 2020/08/11 00:00 [received]
PHST- 2020/11/05 00:00 [accepted]
PHST- 2020/11/04 00:00 [revised]
PHST- 2020/11/24 06:00 [pubmed]
PHST- 2021/10/26 06:00 [medline]
PHST- 2020/11/23 12:10 [entrez]
PHST- 2022/02/01 00:00 [pmc-release]
AID - 10.1007/s00401-020-02244-5 [pii]
AID - 10.1007/s00401-020-02244-5 [doi]
PST - ppublish
SO  - Acta Neuropathol. 2021 Feb;141(2):139-158. doi: 10.1007/s00401-020-02244-5. Epub 
      2020 Nov 23.