The sequencing results from family 3 individual II: 2 revealed a heterozygous frameshift mutation c.2192 delC (p.Pro731LeufsX41) in CDS18 of FBN1 (Figure 3(d)), which caused a translation of the protein to stop at the 771st amino acid residue, by the premature
termination codon (PTC).
To date, 11 mutations of the PLS3 gene have been discovered in BMND18 patients, 7 of which led to premature
termination codon. To understand the molecular repercussions of the mutations related to plastin-3 function, this study reconstructed the WT and 4 mutant structures (2 missense mutations and 2 small insertion mutations) of plastin-3 through homology modelling.
In our study, the mutation type was insertion/duplication in which one base pair duplication leads to alteration of aspartic acid to glutamic acid in codon 112 and subsequently frame-shift mutation occurs which introduces a Premature
Termination Codon (PTC).
The SPLUNC1 cDNA was 1,076 bp long with an open reading frame of 768 bp, which encoded a 26.49 kDa protein composed of 255 amino acids, containing one initiation codon ATG and one
termination codon TAA.
This creates a
termination codon, which is predicted to cause truncation of the SHOX protein at codon 194.
This mutation results in the production of a premature
termination codon (tryptophan[right arrow]stop codon) and gives rise to ([[beta].sup.0]-thalassemia.
In addition to skipping and inclusion of variable exons and usage of alternative splice sites,3 intron retention is a third example of alternative splicing, whereby an intron sequence is retained or skipped in the mature mRNA transcript.4 Notwithstanding intron retention potentially affects mRNA transport to the cytoplasm5 and can insert a premature
termination codon (PTC) and hence its degradation by the terminator (Non-sense mediate mRNA decay),6 there is an evidence for mRNAs that containing intron and are encoding biologically active proteins.4 The markedly increased alternative splicing of genes in human cancers7,8 sheds the light on the possible pathways that might explain the exon containing PCT and whether they are sensitive or resistant to trigger the terminator.9
(3) The novel c.867_945del homozygous deletion in our patient resulted in a frame shift and a premature
termination codon 22 amino acids downstream, p.E289DfsX22.
On the other hand the nonsense mutation in our patient, generated a
termination codon in exon 3 and thus a truncated protein of 46 amino acids, encoding only the N-terminal BRCT domain of the MCPH1 protein.
RB1 Genetic Mutational Analysis of Tumor Sample and Patient's Blood Sample Allele 1 Allele 2 Tumor c.763.C T(R255)X c1572delA Blood c.763.C T(R255)X Normal findings Mutation description Exon 8 causing an Heterozygous deletion immediate termination of the A nucleotide in codon exon 17 Effect on protein
Termination codon A frameshift leading leading to a truncated to a
termination codon nonfunctional Rb and truncated, protein nonfunctional Rb protein Abbreviation: Rb, retinoblastoma.
Hemoglobin Constant Spring and Hb Paske both affect the
termination codon 142, changing it to an amino acid producing an extended protein product that becomes the target of intracellular proteolytic cleavage.