The nonsilent variants at codons 312 (exon10, G>A, Asp312Asn) and 751 (Exon23, A>C, Lys751Gln) are amenable to investigation in epidemiological studies in Caucasians, given their high frequency (Benhamou and Sarasin, 2002).
In total, 11 SNPs of the MGMT gene were identified in that study, including variants at codons 53 and 84 in exon 3, and at codons 143, 178 and 197 in exon 5. Codon 143 is very close to the MGMT active site cysteine-145, and the polymorphism at codon 143 appears to be linked to the codon 178 polymorphism.
Of these 15 tumours, one also had a rare, apparently homozygous, sequence variant at codon 361.
Both patients had a double contiguous variant at codon 112 of the TARDBP gene in exon 3.
The codon 143 variant was a change from I (ATC) to V (GTC), and the variant at codon 178 was from K (AAG) to R (AGG).
The commoner, functionally recessive variant at codon 89 (89*V) was found to be homozygous in two AAD patients but was only found in the heterozygous state in controls.
The genetic variant at codon 129 (M129V) of the prion protein gene (PRNP) is considered to be a major genetic risk factor for prion diseases.
We screened the genomic DNA of 27 patients for CDKN1B germline changes and found a previously unreported variant at codon 69 (c.678C>T, p.P69L) in patient FL, a 79-year-old Caucasian female (Fig. 1A).
The problem is that the variant at codon 2 is not present in all the BAK2 sequences of reference found in the NCBI databank (Fig. 2), which makes very doubtful the validity of the reference sequence for BAK2 and thus the demonstration of Gottlieb et al. [ 2009, 2010].
Indeed, when a GGT→AGT sequence variant at codon 691 is present, there is loss of a BanI restriction site and only one fragment of 408 bp (mutated allele A2) is detected instead of normally two fragments of 185 and 223 bp (wild type allele A1).
