Disorder

Main Symptoms

DNA Repair Defect

Mode of Inheritance

Xeroderma Pigmentosum

Sensitivity to sunlight; slow neurodegeneration; Skin Cancer

NER (7 variants) pol n

Autosomal recessive

Cockayne’s Syndrome

Sensitivity to sunlight; growth retardation; neurological impairment; progeria

Defective NER and TCR

Autosomal recessive

Trichothiodystrophy

Sensitivity to sunlight; dystrophy; short brittle hair with low sulfur content; neurological defects

Defective NER, Particularly of ultraviolet induced damage; closely related to ERCC2 and ERCC3 defects

Autosomal recessive

Down syndrome

Mental retardation; progeria

Defective repair of oxidative DNA damage(trisomy of chromosome 21)

No precise mode of inheritance

Nijmegen breakage syndrome

Progeria; wheel chair dependency

Defective DNA damage response and DSB repair

Autosomal recessive

Alzheimer’s disease

Memory loss; cognitive decline

Increased oxidative stress and damage; defective repair of oxidative damage and DSB repair

Autosomal dominant

Parkinson’s disease

Tremor,bradykinosia,postural rigidity and postural instability

Oxidative Stress and DNA damage; mutations in alfa-synuclein and parkin variants

Autosomal dominant

Huntington’s disease

Progressive chorea and dementia; severe neuronal loss in the striatum and cerebral cortex

CAG repeat expansion in huntingtin(HD) gene and oxidative damage to DNA

Autosomal dominant

Friedreich’s ataxia

Limb ataxia; Sensory loss; skeletal deformities

GAA expanded repeats in frataxin(FXN) gene

Autosomal recessive

Myotonic dystrophy types 1 and 2

Muscle weakness; cataracts; testicular atrophy; cognitive decline

CTG expansion(type 1);CCTG expansion(type 2)

Autosomal dominant

Triple-A syndrome

Adrenal insufficiency;  achalasia; alacrima; neurodegeneration; autonomic dysfunction

Mutation in AAAS gene, which encodes ALADIN protein

Autosomal recessive

Amyotrophic lateral sclerosis

Progressive degeneration of motor neurons; muscle weakness and atrophy, leading to fatality

Defective Cu-Zn superoxide dismutase (SODC; SOD1); Oxidative stress; defective DNA repair (BER?)

Autosomal recessive      

Table 1: Various Neurological Disorder with a link to defective DNA repair