title: Biallelic PMS2 mutations and a distinctive childhood cancer syndrome.
abstract: 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.
authors: Genetic Health Services Victoria, Murdoch Children's Research Institute, Parkville VIC 3052,F Australia.tiong.tan@ghsv.org.au
authors: Tiong Yang
authors: TY
authors: Tan
authors: Lisa M
authors: LM
authors: Orme
authors: Elly
authors: E
authors: Lynch
authors: Matthew A
authors: MA
authors: Croxford
authors: Christopher
authors: C
authors: Dow
authors: Paddy A
authors: PA
authors: Dewan
authors: Lara
authors: L
authors: Lipton
mesh_terms: 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
chemical_list: D004268:DNA-Binding Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D045643:DNA Repair Enzymes