PubMed:9927033 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/9927033","sourcedb":"PubMed","sourceid":"9927033","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/9927033","text":"Human MLH1 deficiency predisposes to hematological malignancy and neurofibromatosis type 1.\nHeterozygous germ-line mutations in the DNA mismatch repair genes lead to hereditary nonpolyposis colorectal cancer. The disease susceptibility of individuals who constitutionally lack both wild-type alleles is unknown. We have identified three offspring in a hereditary nonpolyposis colorectal cancer family who developed hematological malignancy at a very early age, and at least two of them displayed signs of neurofibromatosis type 1 (NF1). DNA sequence analysis and allele-specific amplification in two siblings revealed a homozygous MLH1 mutation (C676T--\u003eArg226Stop). Thus, a homozygous germ-line MLH1 mutation and consequent mismatch repair deficiency results in a mutator phenotype characterized by leukemia and/or lymphoma associated with neurofibromatosis type 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