In genetics , a nonsense mutation is a point mutation in a sequence of DNA that results in a premature stop codon , or a nonsense codon in transcribed mRNA , and in a truncated , incomplete, and generally inert protein product.  The functional effect of a nonsense mutation depends on the location of the stop codon within the coding DNA. 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. 
A nonsense mutation differs from a missense mutation , which is a point mutation where a single nucleotide is changed due to the 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. Some genetic disorders , such as thalassemia and cystic fibrosis  result from nonsense mutations.
DNA : 5′ – ATG Act CAC CGA GCG CGA AGC TGA – 3′ 3′ – TAC TGA GTG GCT CGC GCT TCG Act – 5′ mRNA : 5′ – Aug ACU CAC CGA GCG CGA AGC UGA -3′
Protein: Met Thr His Arg Ala Arg Ser Stop
Suppose a nonsense mutation was introduced in the fourth triplet in the DNA sequence (CGA), which caused cytosine to be replaced with thymine , TGA in the DNA sequence and ACT in the complementary strand. Since ACT is written as UGA and then translated, the resulting transcript and protein product would be:
DNA : 5′ – ATG Act CAC TGA GCG CGA AGC TGA – 3′ 3′ – TAC TGA GTG Act CGC GCT TCG Act – 5′ mRNA : 5′ – Aug ACU CAC UGA GCG CGU AGC UGA -3′
Protein: Met Thr His Stop
The remaining codons of the mRNA are not translated into proteins because the stop codon is reached prematurely during translation. This can generate a truncated (i.e., abridged) protein product, which often lacks the functionality of a normal, non-mutant protein.
Nonsense-mediated mRNA decay
Despite the expected propensity of premature termination codons to yield short polypeptide products, the formation of truly truncated proteins does not occur frequently in vivo . Many organisms—including humans and lower species, such as yeast — employ a nonsense-mediated mRNA decay pathway, which degrades mRNAs containing nonsense mutations before being able to translate them into non-functional polypeptides.
Pathology associated with nonsense mutations
Nonsense mutations can cause a genetic disease by preventing the complete translation of a specific protein. However, the same disease can be caused by other types of damage to the same gene. Examples of diseases in which nonsense mutations cause include:
- Cystic fibrosis (caused by the G542X mutation in the cystic fibrosis transmembrane conductance regulator (CFTR))
- Beta Thalassemia (β-Globin)
- Hurler syndrome
- Dravet syndrome
Ataluren (previously PTC124) is a pharmaceutical drug that can be used to treat genetic diseases caused by nonsense mutations. It is currently being used to treat Duchenne muscular dystrophy.  Clinical trials for the treatment of cystic fibrosis are ongoing.