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High frequency of exon deletions and putative founder effects in French Canadian Lynch syndrome families.
Hum Mutat. 2009 Aug; 30(8):E797-812.HM

Abstract

Lynch syndrome is one of the most common autosomal dominantly inherited cancer syndromes. Mutations in MLH1, MSH2, MSH6, and PMS2 account for greater than 98% of reported mutations in Lynch syndrome families. It has been reported that large genomic deletions in MLH1 and MSH2 are a frequent cause of Lynch syndrome in certain populations. Using a multimodal approach, we have identified mutations in MLH1, MSH2, and MSH6 in French Canadian families fulfilling the Amsterdam criteria for Lynch syndrome and who displayed abnormal staining for at least one of the Lynch syndrome proteins. Mutations were identified in 28 of our 29 French Canadian probands (97%). A total of 18 distinct mutations (nine in MLH1, seven in MSH2, two in MSH6) were identified, of which six (33%) were genomic exon deletions. Another four (22%) resulted in exon deletions in cDNA alone. Three (17%) are novel mutations. Five of these 18 mutations were detected in more than one distinct family (four in MLH1, one in MSH2) and haplotype analysis suggests the possibility of founder effects. Fifteen of the 29 (52%) families carried one of these five putative founder mutations. These findings may simplify genetic testing for Lynch syndrome in French Canadians.

Authors+Show Affiliations

Departments of Medical Genetics and Oncology, Cancer Prevention Centre, Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19459153

Citation

Chong, George, et al. "High Frequency of Exon Deletions and Putative Founder Effects in French Canadian Lynch Syndrome Families." Human Mutation, vol. 30, no. 8, 2009, pp. E797-812.
Chong G, Jarry J, Marcus V, et al. High frequency of exon deletions and putative founder effects in French Canadian Lynch syndrome families. Hum Mutat. 2009;30(8):E797-812.
Chong, G., Jarry, J., Marcus, V., Thiffault, I., Winocour, S., Monczak, Y., Drouin, R., Latreille, J., Australie, K., Bapat, B., Gordon, P. H., Giguère, Y., Gologan, A., Galiatsatos, P., Jass, J. R., Wong, N., Zaor, S., Palma, L., Kasprzak, L., ... Foulkes, W. D. (2009). High frequency of exon deletions and putative founder effects in French Canadian Lynch syndrome families. Human Mutation, 30(8), E797-812. https://doi.org/10.1002/humu.21056
Chong G, et al. High Frequency of Exon Deletions and Putative Founder Effects in French Canadian Lynch Syndrome Families. Hum Mutat. 2009;30(8):E797-812. PubMed PMID: 19459153.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High frequency of exon deletions and putative founder effects in French Canadian Lynch syndrome families. AU - Chong,George, AU - Jarry,Jonathan, AU - Marcus,Victoria, AU - Thiffault,Isabelle, AU - Winocour,Sebastian, AU - Monczak,Yury, AU - Drouin,Régen, AU - Latreille,Jean, AU - Australie,Karlene, AU - Bapat,Bharati, AU - Gordon,Philip H, AU - Giguère,Yves, AU - Gologan,Adrian, AU - Galiatsatos,Polymnia, AU - Jass,Jeremy R, AU - Wong,Nora, AU - Zaor,Sonya, AU - Palma,Laura, AU - Kasprzak,Lidia, AU - Tischkowitz,Marc, AU - Foulkes,William D, PY - 2009/5/22/entrez PY - 2009/5/22/pubmed PY - 2009/10/23/medline SP - E797 EP - 812 JF - Human mutation JO - Hum Mutat VL - 30 IS - 8 N2 - Lynch syndrome is one of the most common autosomal dominantly inherited cancer syndromes. Mutations in MLH1, MSH2, MSH6, and PMS2 account for greater than 98% of reported mutations in Lynch syndrome families. It has been reported that large genomic deletions in MLH1 and MSH2 are a frequent cause of Lynch syndrome in certain populations. Using a multimodal approach, we have identified mutations in MLH1, MSH2, and MSH6 in French Canadian families fulfilling the Amsterdam criteria for Lynch syndrome and who displayed abnormal staining for at least one of the Lynch syndrome proteins. Mutations were identified in 28 of our 29 French Canadian probands (97%). A total of 18 distinct mutations (nine in MLH1, seven in MSH2, two in MSH6) were identified, of which six (33%) were genomic exon deletions. Another four (22%) resulted in exon deletions in cDNA alone. Three (17%) are novel mutations. Five of these 18 mutations were detected in more than one distinct family (four in MLH1, one in MSH2) and haplotype analysis suggests the possibility of founder effects. Fifteen of the 29 (52%) families carried one of these five putative founder mutations. These findings may simplify genetic testing for Lynch syndrome in French Canadians. SN - 1098-1004 UR - https://www.unboundmedicine.com/medline/citation/19459153/High_frequency_of_exon_deletions_and_putative_founder_effects_in_French_Canadian_Lynch_syndrome_families_ L2 - https://doi.org/10.1002/humu.21056 DB - PRIME DP - Unbound Medicine ER -