The inframe MSH2 codon 596 deletion is linked with HNPCC and associated with lack of MSH2 protein in tumours.
Hereditary nonpolyposis colorectal cancer (HNPCC) may be caused by germline truncating mutations in DNA mismatch repair (MMR) genes. Whether or not missense or inframe mutations are disease-associated has become a practical clinical problem, because predictive genetic testing is employed to select high-risk persons for clinical examinations. Clinical examinations may reveal polyps to be removed and prevent cancer. One large kindred applying for health care had a N596del mutation in the MSH2 gene. The aim of this study was to determine whether or not the inframe mutation in this family was associated with disease, and to examine the tumours for presence of the MSH2 protein by immunohistochemistry. We demonstrated that the mutation was linked to disease with lod score 5.7 in the family, and all examined, but one manifest cancer, lacked the MSH2 protein.
Stormorken
Astrid T
AT
Section of Genetic Counselling, Department of Cancer Genetics, The Norwegian Radium Hospital, Oslo, Norway.
Müller
Wolfram
W
Lindblom
Annika
A
Heimdal
Ketil
K
Aase
Steinar
S
Lothe
Inger Marie Bowitz
IM
Norèn
Tove
T
Wijnen
Juul T
JT
Möslein
Gabriela
G
Møller
Pål
P
D000251:Adenosine Triphosphatases; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020137:Base Pair Mismatch; D003062:Codon; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000473:pathology*; D004260:DNA Repair; D004268:DNA-Binding Proteins; D005260:Female; D016368:Frameshift Mutation; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D051718:MutS Homolog 2 Protein; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*
D003062:Codon; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D000251:Adenosine Triphosphatases; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein