Polymorphisms in a pseudogene highly homologous to PMS2.
PMS2 is one of a complex of genes encoding DNA repair proteins that includes MSH2, MLH1, MSH6 and MSH3. Mutation of any of these DNA mismatch repair genes leads to impairment of DNA repair and can lead to tumorigenesis. Germline mutation of PMS2 has been reported as a rare cause of hereditary nonpolyposis colorectal cancer (HNPCC) and Turcot's syndrome. The PMS2 gene is located on chromosome 7p22 and consists of 15 exons. Within exon 11 of PMS2 is a coding repeat of eight adenosines. This study reports on the finding of a nonexpressed pseudogene that is highly homologous to the PMS2 gene in this region. The pseudogene is polymorphic for two alterations in the repeat region: a 3 bp delAAA at a site corresponding to nucleotide 1231 in PMS2; and an AA-->GG change at nucleotide 1238. Due to the high homology in both intronic and exonic sequences, polymorphisms in this pseudogene could be mistaken for mutations in the PMS2 gene and erroneously thought to be a cause of HNPCC and/or Turcot's syndrome.
Chadwick
R B
RB
Division of Human Cancer Genetics, The Ohio State University, Columbus, Ohio, USA.
Meek
J E
JE
Prior
T W
TW
Peltomaki
P
P
de La Chapelle
A
A
D000251:Adenosine Triphosphatases; D020137:Base Pair Mismatch / Q000235:genetics; D001483:Base Sequence; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D000070976:Mismatch Repair Endonuclease PMS2; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011544:Pseudogenes / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid
D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D045643:DNA Repair Enzymes