Genetic Counseling for TP53 Germline Mutations

摘要: Li–Fraumeni syndrome (LFS; OMIM # 151623) is an autosomal dominant disorder associated with multiple early-onset cancers. Classic LFS and its variants, collectively named Li–Fraumeni-like (LFL) syndrome, are two recognized forms of the syndrome. It estimated that carriers a germlineTP53 mutation have, on average, 50 % risk to develop cancer before age 40 years life 90 %. Clinical management individuals LFS/LFL major challenge due wide tumor spectrum. Monitoring strategies have shown reduce mortality in TP53 germline mutations. Cancer-prone families Southeastern Brazil been identified carry founder (c.1010G>A, p.R337H) at unusually high prevalence about 1:300 subjects (0.3 %). Structural functional studies p.R337H mutant proteins vitro pH-dependent defect oligomerization domain, making them inactive only conditions increased intracellular pH. The allele unique example pathogenic persisting among large mixed population. Genetic counseling should integrate clinical assessment care all carrying complexity diagnosis prognostic definitions, as well long-term impact being diagnosed their relatives, calls for multidisciplinary approach counseling, involving health professionals from areas expertise.