IV. NER and Human genetic diseases

 

The genes encoding many of the human  NER proteins were first identified in genetic complementation studies of the human DNA repair disease. Xeroderma pigmentosum (XP), which suggested that mutations in any of 7 genes (XPA-XPG) could give rise to the disease. In addition to XP, two other human genetic diseases involve defects in or related to nucleotide excision repair. These two additional diseases involve are Cockayne’s syndrome (CS) and trichothiodystrophy (TTD). Although all 3 diseases are associated with repair defects, they have strikingly different clinical manifestations:

 

Patients suffering from XP have

 

·       Severe light sensitivity

·       Severe pigmentation irregularities

·       Frequent neurological defects

·       Early onset of skin cancer at high incidence

·       Elevated frequency of other forms of cancer

 

Cockayne’s syndrome gives rise to

 

·       Dwarfism

·       Light sensitivity in some cases

·       Facial and limb abnormalities

·       Neurological abnormalities

·       Early death due to neurodegeneration

 

 

Trichothiodystrophy patients display

 

·       Sulfur deficient brittle hair

·       Facial abnormalities

·       Short stature

·       Ichthyosis (fish-like scales on the skin)

·       Light sensitivity in about 50% of cases