Furthermore, a start codon mutation has been identified in a French family (Met1_AAG mutation, TPI Paris) as well as a frame shift mutation at codon 28 or mutations within the upstream region of the TPI gene [3], [17].
Direct sequencing of BRCA2 coding exons of patients carrying the shared haplotype, allowed the identification of a 'frame-shift' mutation at codon 2867 (8765delAG), causing a premature termination-codon.
In more than 200 samples lung, breast, kidney and nasopharyngeal carcinomas and cell lines analysed, only one frame-shift mutation (at codon 277 in the RA domain) and one missense mutation (at codon 201 in the RA domain) have been identified [13,16,39 41].
This would result in a frame shift and premature termination at codon 306 that would yield an inactivate p53.
When compared with the wild-type PanD protein, the majority of the mutants (24 of 30 or 80%) had the M117I mutation, and the remaining 6 had the mutations L136R, V138G, V138E, V138A, E126* and a codon shift at 131 (Table 1 and Figure 1).
The c.2475delC mutation (BIC 2594delC) is a frame-shift deletion, resulting in termination at codon 845.
One interpretation of these divergence patterns is that there has been a shift of codon preference, such that AT-ending codons are on average beneficial (whereas GC-ending codons were ancestrally favored).
The c.1954dupA (BIC 2080insA) mutation is a frame-shift causing insertion, resulting in termination of transcription at codon 672 and has been reported as a Pakistani founder mutation (Liede et al, 2002).
The frame shift mutation c.211dupA results in a premature protein termination at codon 79.
One alternate transcript involved the deletion of exon 10 (117bp.Gly1000_Gly1038del3del, p.Gly1000_Gly1038del), and the other included a 31bp deletion in exon 10 (p.Gly1028fs*33113del, p.Gly1028fs*3) that resulted in a shift of reading frame and a premature termination codon (PTC) (at codon 1030).
