A novel exonic rearrangement affecting MLH1 and the contiguous LRRFIP2 is a founder mutation in Portuguese Lynch syndrome families

• Type: Article in International Scientific Journal
• Date: 2011

Authors

Pinheiro, M (Author) Other; Pinto, C (Author) Other; Peixoto, A (Author) Other; Veiga, I (Author) Other; Mesquita, B (Author) Other; henrique, rmf (Author) ICBAS; Baptista, M (Author) Other; Fragoso, M (Author) Other; Sousa, O (Author) Other; Pereira, H (Author) Other; Marinho, C (Author) Other; Dias, LM (Author) Other; Manuel R Teixeira (Author) ICBAS

Journal

Title: Genetics in Medicine

Vol. 13

Pages: 895-902

ISSN: 1098-3600

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 20 Citations

Scopus - 20 Citations

Other information

Authenticus ID: P-002-M0D

DOI: 10.1097/gim.0b013e31821dd525

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8