期刊
GENETICS IN MEDICINE
卷 13, 期 10, 页码 895-902出版社
NATURE PUBLISHING GROUP
DOI: 10.1097/GIM.0b013e31821dd525
关键词
MLH1; LRRFIP2; exonic rearrangement; founder mutation; Lynch syndrome
资金
- Portuguese Health Ministry
- Liga Portuguesa Contra o Cancro
Purpose: Although Lynch syndrome is characterized by marked genetic heterogeneity, some specific mutations are observed at high frequency in well-defined populations or ethnic groups due to founder effects. Methods: Genomic breakpoint identification, haplotype analysis, and mutation age determination were performed in 14 unrelated patients and 95 family members presenting the same MLH1 exonic rearrangement, among a series of 84 Lynch syndrome families with germline mutations in MLH1, MSH2, or MSH6. Results: All 14 probands harbored an identical deletion, comprising exons 17-19 of the MLH1 gene and exons 26-29 of the LRRFIP2 gene, corresponding to the MLH1 mutation c. 1896 + 280_oLRRFIP2: c. 1750-678del. This mutation represents 17% of all deleterious mismatch repair mutations in our series. Haplotype analysis showed a conserved region of approximately 1 Mb, and the mutation age was estimated to be 283 +/- 78 years. All 14 families are originated from the Porto district countryside. Conclusion: We have identified a novel MLH1 exonic rearrangement that is a common founder mutation in Lynch syndrome families, indicating that screening for this rearrangement as a first step may be cost-effective during genetic testing of Lynch syndrome suspects of Portuguese ancestry, especially those originating from the Porto district. Genet Med 2011:13(10):895-902.
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