These authors contributed equally.
Germ line MLH1 and MSH2 mutations in Taiwanese Lynch syndrome families: characterization of a founder genomic mutation in the MLH1 gene
Version of Record online: 15 APR 2009
© 2009 John wiley & sons A/S
Volume 75, Issue 4, pages 334–345, April 2009
How to Cite
Tang, R., Hsiung, C., Wang, J.-Y., Lai, C.-H., Chien, H.-T., Chiu, L.-L., Liu, C.-T., Chen, H.-H., Wang, H.-M., Chen, S.-X., Hsieh, L.-L. and the TCOG HNPCC Consortium (2009), Germ line MLH1 and MSH2 mutations in Taiwanese Lynch syndrome families: characterization of a founder genomic mutation in the MLH1 gene. Clinical Genetics, 75: 334–345. doi: 10.1111/j.1399-0004.2009.01162.x
- Issue online: 15 APR 2009
- Version of Record online: 15 APR 2009
- Received 22 August 2008, revised and accepted for publication 15 December 2008
- founder mutation;
- Lynch syndrome;
- mutation/large deletion
This multicenter study evaluated the mutation spectrum and frequencies of the MLH1 and MSH2 genes and determined the occurrence of large genomic deletions in 93 unrelated Taiwanese families that fulfilled the Amsterdam criteria II by denaturing high-performance liquid chromatography analysis, DNA sequencing for aberrant chromatograms, and multiplex ligation-dependent probe amplification analysis. In total, 38 pathogenic mutations (10 large deletions and 28 point mutations or small deletion/insertions) in the MSH2 or MLH1 gene were identified in 61 of the 93 families (66%). Three of the 10 large deletions and 14 of the 28 point mutations or small insertions/deletions have not been reported elsewhere. Three mutations in the MLH1 gene, the MLH1c.1846_1848delAAG (5 families), deletion exons 11–15 (4 unrelated families), and MLH1c.793C>T (13 unrelated families), accounted for 35% of all cases with pathogenic mutations. Haplotype analysis indicated that mutant c.793C>T alleles were derived from two distinct common founders that might be inherited from a single ancestor of presumably Chinese origin. As a mutation detection strategy for Taiwanese Lynch syndrome patients, we recommend that diagnosis starts with screening for large genomic deletions and continues by screening for common mutations in exons 10 and 16 of the MLH1 gene prior to searching for small mutations in the remaining exons.