J Genet Med.  2016 Jun;13(1):1-13. 10.5734/JGM.2016.13.1.1.

DNA damage to human genetic disorders with neurodevelopmental defects

• Lee Y
• Choi I
• Kim J
• Kim K

• KMID: 2327696
• DOI: http://doi.org/10.5734/JGM.2016.13.1.1

Abstract

Although some mutations are beneficial and are the driving force behind evolution, it is important to maintain DNA integrity and stability because it contains genetic information. However, in the oxygen-rich environment we live in, the DNA molecule is under constant threat from endogenous or exogenous insults. DNA damage could trigger the DNA damage response (DDR), which involves DNA repair, the regulation of cell cycle checkpoints, and the induction of programmed cell death or senescence. Dysregulation of these physiological responses to DNA damage causes developmental defects, neurological defects, premature aging, infertility, immune system defects, and tumors in humans. Some human syndromes are characterized by unique neurological phenotypes including microcephaly, mental retardation, ataxia, neurodegeneration, and neuropathy, suggesting a direct link between genomic instability resulting from defective DDR and neuropathology. In this review, rare human genetic disorders related to abnormal DDR and damage repair with neural defects will be discussed.

Keyword

DNA damage; DNA repair; Single-stranded DNA breaks; Double-stranded DNA breaks; Central nervous system diseases

MeSH Terms

Aging
Aging, Premature
Ataxia
Cell Cycle Checkpoints
Cell Death
Central Nervous System Diseases
DNA Breaks, Double-Stranded
DNA Breaks, Single-Stranded
DNA Damage*
DNA Repair
DNA*
Genomic Instability
Humans*
Immune System
Infertility
Intellectual Disability
Microcephaly
Neuropathology
Phenotype
DNA