A 10-Year Review on Advancements in Identifying and Treating Intellectual Disability Caused by Genetic Variations
Abstract
:1. Introduction
2. Identification
3. Physiological Basis
4. Genetic Etiology of ID
4.1. Autosomal Dominant ID
4.2. Autosomal Recessive ID
4.3. XLID
5. Treatment
5.1. General Treatment
5.2. Genetic Therapy
5.3. Exercise Therapy
6. Conclusions and Outlook
Author Contributions
Funding
Conflicts of Interest
References
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Name | Catalog | Advantages | Disadvantages |
---|---|---|---|
Sanger sequencing | A long sequencing length (1 kb) and a high accuracy rate of 100% | Time consuming (weeks or even months of work) and expensive (millions of dollars), requires known genomic loc | |
Next-generation Sequencing (NGS) | Whole-exome sequencing (WES) | Short turnaround time (only days or weeks of work), low cost (thousands of dollars), and high diagnostic rate (millions of reads) | Can only search DNA sequences in the exonic regions |
Whole-genome sequencing (WGS) | Captures both exonic and intronic regions, identifies pathogenic variations in complex genes, and improves de novo mutations detection | Short reads (400 bp or 2 × 300 bp) | |
Third-generation sequencing (TGS) | Overcomes the biases-related issues introduced by PCR amplification and dephasing and increases the length of base reads | High error rate during sequencing (an error rate of 10–20%) |
Gene | Pathogenesis | Phenotype |
---|---|---|
MECP2 | abnormal transcriptional regulation and chromatin remodeling | Immature and decreased synapse numbers Impaired synaptic plasticity (e.g., LTP ↓) Decreased dendritic density Dendritic spine immature and decreased spine numbers |
UBE3A | affecting the ubiquitin-proteasome pathway | |
DYRK1A | abnormal encode a kinase involved in brain development | |
PTEN | dysregulated cell growth and proliferation | |
TCE4 | abnormal transcriptional regulation | |
GNAS | abnormal G protein signaling | |
CHD8 | disrupt chromatin remodeling and gene expression | |
KDM5C | affect a neurodevelopmental kinase | |
PHF | neurodevelopmental gene expression dysregulation | |
EHMT1 | neurodevelopmental gene expression dysregulation | |
NF1 | dysregulated cell growth and proliferation | |
ZDHHC9 | abnormal protein palmitoylation | |
ATRX | chromosomal abnormalities and defective DNA repair | |
FOXP1 | abnormal transcriptional regulation | |
FMR1 | impaired FMRP protein production | |
TSC1/TSC2 | abnormal cell growth and proliferation | |
CDKL5 | affect a neurodevelopmental kinase | |
TRAPPC9 | affects nerve growth factor-induced neuronal differentiation | |
USUN2 | decreased tRNA methyltransferase function | |
SHANK3 | abnormal postsynaptic protein density | Impaired synaptic plasticity (e.g., LTP↓) Abnormal neuronal signaling |
SYNGAP1 | de novo variations in certain proteins | |
NRXN1 | abnormal presynaptic protein synthesis | |
SCN2A | sodium channel dysfunction | |
CACNA1A | calcium channel dysfunction | |
STXBP1 | dysfunction of neurotransmitter release process | |
GRIN2B | NMDA receptor dysfunction | |
GABRA1 | GABA receptor dysfunction |
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Hou, K.; Zheng, X. A 10-Year Review on Advancements in Identifying and Treating Intellectual Disability Caused by Genetic Variations. Genes 2024, 15, 1118. https://doi.org/10.3390/genes15091118
Hou K, Zheng X. A 10-Year Review on Advancements in Identifying and Treating Intellectual Disability Caused by Genetic Variations. Genes. 2024; 15(9):1118. https://doi.org/10.3390/genes15091118
Chicago/Turabian StyleHou, Kexin, and Xinyan Zheng. 2024. "A 10-Year Review on Advancements in Identifying and Treating Intellectual Disability Caused by Genetic Variations" Genes 15, no. 9: 1118. https://doi.org/10.3390/genes15091118