Somatic mosaicism: A common cause of classic disease in tumor-prone syndromes? Lessons from type 2 neurofibromatosis

Gareth Evans, D. G R Evans, A. J. Wallace, C. L. Wu, L. Trueman, R. T. Ramsden, T. Strachan

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Blood samples from 125 families with classic type 2 neurofibromatosis with bilateral vestibular schwannomas were analyzed for mutations in the NF2 gene. Causative mutations were identified in 52 families. In five families, the first affected individual in the family (the index case) was a mosaic for a disease-causing mutation. Only one of nine children from the three mosaic cases with children are affected. Four of these nine children inherited the allele associated with the disease-causing mutation yet did not inherit the mutation. NF2 mutations were identified in only 27/79 (34%) of sporadic cases, compared with 25/46 (54%) of familial cases (P <.05). In 48 families in which a mutation has not been identified, the index cases have had 125 children, of whom only 29 are affected with NF2 and of whom only a further 21 cases would be predicted to be affected by use of life curves. The 50/125 (40%) of cases is significantly less than the 50% expected eventually to develop NF2 (P <.05). Somatic mosaicism is likely to be a common cause of classic NF2 and may well account for a low detection rate for mutations in sporadic cases. Degrees of gonosomal mosaicism mean that recurrence risks may well be
    Original languageEnglish
    Pages (from-to)727-736
    Number of pages9
    JournalAmerican Journal of Human Genetics
    Volume63
    Issue number3
    DOIs
    Publication statusPublished - Sept 1998

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