Nonsense mutation

In genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a nonsense codon, or a premature stop codon in the transcribed mRNA, and leads to a truncated, incomplete, and possibly nonfunctional protein product.^[1] Nonsense mutations are not always harmful;^[2] the functional effect of a nonsense mutation depends on many aspects, such as the location of the stop codon within the coding DNA.^[2] For example, the effect of a nonsense mutation depends on the proximity of the nonsense mutation to the original stop codon, and the degree to which functional subdomains of the protein are affected.^[3] As nonsense mutations leads to premature termination of polypeptide chains; they are also called chain termination mutations.^[4]

Missense mutations differ from nonsense mutations since they are point mutations that exhibit a single nucleotide change to cause substitution of a different amino acid. A nonsense mutation also differs from a nonstop mutation, which is a point mutation that removes a stop codon. About 10% of patients facing genetic diseases have involvement with nonsense mutations.^[5] Some of the diseases that these mutations can cause are Duchenne muscular dystrophy (DMD), cystic fibrosis (CF),^[6] spinal muscular atrophy (SMA), cancers, metabolic diseases, and neurologic disorders.^[5][7] The rate of nonsense mutations is variable from gene-to-gene and tissue-to-tissue, but gene silencing occurs in every patient with a nonsense mutation.^[5]