Molecular lesions that abrogate gene function

(abrogate = officially cancel, annul, or abolish something)

Splice site mutation

Splice site mutations frequently result in the production of larger proteins with altered function but preserved immune reactivity.

Deletion

• Removal of entire gene
  • E.g. alpha-thalassaemia, completement C4A deficiency
• Excision of part of a gene -> may cause additional frameshift
  • E.g. X-linked muscular dystrophies
• Removal of a single codon
  • E.g. Delta-F508 (DF508) mutation in cystic fibrosis

Cri-du-chat (cry of the cat) syndrome

deletion of 5p

other features:

hypotonia, short stature, microcephaly with protruding metopic suture, moon-like face, hypertelorism, bilateral epicanthal folds, high arched palate, wide and flat nasal bridge and mental retardation

Insertion

• Insertion of LINE-1 element
  • E.g. F8 gene in haemophilia A
• Triplet repeats
  • E.g. Myotonic dystrophy, etc. (See others: triplet repeat and anticipation)

Nonsense mutation

• Base change creating new stop codon
  • E.g. (A->T) transversion in beta-globin codon 6 causing E -> V

Missense mutation