Recent genome-wide analyses have detected numerous cancer-specific alternative splicing (AS) events. Whether transcripts containing cancer-specific AS events are likely to be translated into functional proteins or simply reflect noisy splicing, thereby determining their clinical relevance, is not known. Here we show that consistent with a noisy-splicing model, cancer-specific AS events generall...

Premature stop codons in CACNA1A, which encodes the alpha(1A) subunit of neuronal P/Q-type (Ca(V)2.1) Ca(2+) channels, cause episodic ataxia type 2 (EA2). CACNA1A undergoes extensive alternative splicing, which contributes to the pharmacological and kinetic heterogeneity of Ca(V)2.1-mediated Ca(2+) currents. We identified three novel heterozygous stop codon mutations associated with EA2 in an a...

The spinocerebellar ataxia recessive type 10 is a genetic form associated with ANO10 gene mutations. Affected individuals present ataxia, hyperreflexia, ocular movement disorders and cerebellar atrophy. homozygous variant in the NP_060545.3:p.Asn114* 2-nucleotide deletion that would cause introduction of premature stop codon at same position, has not been previously described scientific literat...

Somatic hypermutation, in addition to V(D)J recombination, is the other major mechanism that generates the vast diversity of the Ab repertoire. Point mutations are introduced in the variable region of the Ig genes at a million-fold higher rate than in the rest of the genome. We have used a green fluorescent protein (GFP)-based reversion assay to determine the role of transcription in the mutati...

The presence in the mRNA of premature stop codons (PTCs) results in protein truncation responsible for several inherited (genetic) diseases. A well-known example of these diseases is cystic fibrosis (CF), where approximately 10% (worldwide) of patients have nonsense mutations in the CF transmembrane regulator (CFTR) gene. PTC124 (3-(5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)-benzoic acid), also k...

Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene, leading to the absence of the dystrophin protein in striated muscle. A significant number of these mutations are premature stop codons. On the basis of the observation that aminoglycoside treatment can suppress stop codons in cultured cells, we tested the effect of gentamicin on cultured muscle cells from the mdx m...

A new study reports the presence of a chemosensory pseudogene in Drosophila sechellia, which in spite of carrying a premature stop-codon nevertheless encodes a fully functional and full-length protein. Such 'pseudo-pseudogenes' might well be a widespread phenomenon.

Papillon-Lefèvre syndrome (PLS) is an autosomal recessive disorder characterised by palmoplantar hyperkeratosis and severe early onset periodontitis that results in the premature loss of the primary and secondary dentitions. A major gene locus for PLS has been mapped to a 2.8 cM interval on chromosome 11q14. Correlation of physical and genetic maps of this interval indicate it includes at least...

N onsense mutations located in the 59 end of the coding sequence of a gene are commonly considered to be null alleles. Not only do such mutations result in the production of a truncated and usually inactive protein product, but premature stop codon mutations that occur upstream of the last exon–exon junction are also known to activate nonsense mediated decay (NMD) which results in the specific ...

Papillon-Lefèvre syndrome (PLS) is an autosomal recessive disorder characterised by palmoplantar hyperkeratosis and severe early onset periodontitis that results in the premature loss of the primary and secondary dentitions. A major gene locus for PLS has been mapped to a 2.8 cM interval on chromosome 11q14. Correlation of physical and genetic maps of this interval indicate it includes at least...