Biallelic PMS2 mutations and a distinctive childhood cancer syndrome.
Biallelic mutations in PMS2, a gene usually associated in heterozygous form with hereditary nonpolyposis colorectal cancer (HNPCC), results in a recently described childhood cancer syndrome. The tumor spectrum encompasses atypical brain cancers, hematologic malignancies, and colonic polyposis and cancer. Cutaneous stigmata resembling café-au-lait macules with more diffuse margins are frequently seen. Onset is as young as 2 years. The risk of second malignancy is high. Evidence exists for surveillance for bowel cancer, but surveillance for the wider tumor spectrum is of uncertain benefit. We report a consanguineous Australian-Lebanese family with multiple affected individuals shown to be homozygous for a PMS2 exon 7 deletion. We also review published cases of biallelic mutations in HNPCC-related genes. Early recognition of this familial cancer syndrome is critical, and should prompt investigation for familial HNPCC mutations.
Tan
Tiong Yang
TY
Genetic Health Services Victoria, Murdoch Children's Research Institute, Parkville VIC 3052,F Australia.tiong.tan@ghsv.org.au
Orme
Lisa M
LM
Lynch
Elly
E
Croxford
Matthew A
MA
Dow
Christopher
C
Dewan
Paddy A
PA
Lipton
Lara
L
D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D002648:Child; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D003241:Consanguinity; D053843:DNA Mismatch Repair; D045643:DNA Repair Enzymes / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D017809:Fatal Outcome; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D000070976:Mismatch Repair Endonuclease PMS2; D020125:Mutation, Missense; D009378:Neoplasms, Multiple Primary / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D017384:Sequence Deletion; D013577:Syndrome
D004268:DNA-Binding Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D045643:DNA Repair Enzymes