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. 2013 Dec 18;11(1):18.
doi: 10.1186/1897-4287-11-18.

Mutation spectrum in South American Lynch syndrome families

Mev Dominguez-Valentin  1 , Mef Nilbert, Patrik Wernhoff, Francisco López-Köstner, Carlos Vaccaro, Carlos Sarroca, Edenir Ines Palmero, Alejandro Giraldo, Patricia Ashton-Prolla, Karin Alvarez, Alejandra Ferro, Florencia Neffa, Junea Caris, Dirce M Carraro, Benedito M Rossi
Affiliations

Mutation spectrum in South American Lynch syndrome families

Mev Dominguez-Valentin et al. Hered Cancer Clin Pract. .

Abstract

Background: Genetic counselling and testing for Lynch syndrome have recently been introduced in several South American countries, though yet not available in the public health care system.

Methods: We compiled data from publications and hereditary cancer registries to characterize the Lynch syndrome mutation spectrum in South America. In total, data from 267 families that fulfilled the Amsterdam criteria and/or the Bethesda guidelines from Argentina, Brazil, Chile, Colombia and Uruguay were included.

Results: Disease-predisposing mutations were identified in 37% of the families and affected MLH1 in 60% and MSH2 in 40%. Half of the mutations have not previously been reported and potential founder effects were identified in Brazil and in Colombia.

Conclusion: The South American Lynch syndrome mutation spectrum includes multiple new mutations, identifies potential founder effects and is useful for future development of genetic testing in this continent.

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Figures

Figure 1
Figure 1
Flowchart of South American patients/families included in the study.
Figure 2
Figure 2
Spectrum of pathogenic mutations in MLH1 and MSH2 genes a) Types of pathogenic germline mutations; b) Distribution along all exons of the MMR genes.
Figure 3
Figure 3
Map of South America showing the countries where Lynch syndrome families with the founder, recurrent, unique mutations and variants of unclassified significance (VUS) have been identified. The figure depicts the countries participating in the study (gray). The pie chart represents in percentage the recurrent mutations, unique mutations, founder mutations and VUS identified in the South American families. Brazil is characterized by 16% of the founder mutations, 39% of the recurrent mutations, 14% of the unique mutations and 31% of the VUS, while Colombia by 20% of the founder mutations, 20% of the unique mutations and 60% of the VUS. Chile, Argentina and Uruguay are characterized by 80%, 50% and 67% of the recurrent mutations and 20%, 50% and 33% of the VUS, respectively.
See this image and copyright information in PMC

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