We report on a female patient diagnosed with breast, colon, and endometrial cancer at the age of 38, 40, and 41 respectively, presenting with café au lait macules, multiple neurofibromas and axillary freckling. With respect to the family history, her paternal grandmother died at the age of 63 for a colon cancer diagnosed when she was 35, whereas her father died at the age of 42 because of an accident. As the proband met the criteria for Neurofibromatosis 1 (NF1), analysis of the NF1 gene was performed. A frameshift mutation (c.7096_7101delAACTTT) was identified confirming the clinical diagnosis. The parents showed no clinical signs of NF1 nor did the two proband‘s siblings, which tested negative. Because of the co-occurrence of endometrial and colon cancer in our patient, and the presence of an early-onset colon cancer in the paternal grandmother, expression of mismatch repair protein and Microsatellite Instability (MSI) were analyzed on endometrial and colon cancers. Both tissue showed loss of staining for the MSH2-MSH6 heterodimer and high MSI, therefore analysis of MSH2 was performed, leading to the identification of a nonsense mutation of exon 2 (c.289C>T, p.Gln97*), consistent with the presence of the Lynch syndrome. As women with NF1 have a fivefold risk of developing premenopausal breast cancer, no further analysis was performed. Although it was not possible to analyze any member of the paternal family, an intriguing possibility is that the inherited germinal mutation affecting the mismatch repair system led to a de novo NF1 germinal mutation in our patient.
A germline mismatch repair mutation possibly leading to a de novo NF1 germline mutation. / Bracco C; Borelli I; Micheletti M; Martorana D;Grosso E; Pasini B. - In: EUROPEAN JOURNAL OF HUMAN GENETICS. - ISSN 1018-4813. - ELETTRONICO. - 22:Supplement 1, May 2014(2014), pp. 256-256. ((Intervento presentato al convegno European Human Genetics Conference 2014 tenutosi a Milan, Italy nel May 31 - June 3, 2014.