Genomic and functional analyses of MUTYH in Japanese patients with adenomatous polyposis

R. Yanaru-Fujisawa, T. Matsumoto, Y. Ushijima, M. Esaki, M. Hirahashi, M. Gushima, T. Yao, Y. Nakabeppu, M. Iida

Research output: Contribution to journalArticle

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Abstract

The present study was undertaken to elucidate germ line mutations of the base excision repair gene, MUTYH, in Japanese patients with adenomatous polyposis. We screened germ line mutations of adenomatous polyposis coli (APC) gene and MUTYH in 66 Japanese patients with adenomatous polyposis. APC was screened by the protein truncation test, while MUTYH was screened by polymerase chain reaction-based single-strand conformation polymorphism and direct sequencing. The nicking assay was applied in order to evaluate the DNA glycosylase activity of the identified MUTYH variant. In this study, Seven MUTYH variants were identified in 16 of 21 APC-negative patients. Q324H mutation was the most frequent mutation, with an allele frequency of 49%. Two patients carried biallelic mutations other than Q324H; a patient had biallelic G272E and A359V mutations, while the other had compound heterozygotes of P18L and G25D mutations. Nicking assay for G272E using the corresponding mouse MUTYH mutant with G257E revealed that G272E is a variant to cause an impaired DNA glycosylase activity. Homozygous MUTYH mutation accounts for approximately 10% of Japanese patients with adenomatous polyposis. G272E may be one of the mutations specific to patients with adenomatous polyposis in East Asia.

Original languageEnglish
Pages (from-to)545-553
Number of pages9
JournalClinical Genetics
Volume73
Issue number6
DOIs
Publication statusPublished - Jun 1 2008

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Mutation
DNA Glycosylases
Adenomatous Polyposis Coli
Germ-Line Mutation
APC Genes
Far East
Heterozygote
Gene Frequency
DNA Repair
Polymerase Chain Reaction
Genes
Proteins

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Yanaru-Fujisawa, R., Matsumoto, T., Ushijima, Y., Esaki, M., Hirahashi, M., Gushima, M., ... Iida, M. (2008). Genomic and functional analyses of MUTYH in Japanese patients with adenomatous polyposis. Clinical Genetics, 73(6), 545-553. https://doi.org/10.1111/j.1399-0004.2008.00998.x

Genomic and functional analyses of MUTYH in Japanese patients with adenomatous polyposis. / Yanaru-Fujisawa, R.; Matsumoto, T.; Ushijima, Y.; Esaki, M.; Hirahashi, M.; Gushima, M.; Yao, T.; Nakabeppu, Y.; Iida, M.

In: Clinical Genetics, Vol. 73, No. 6, 01.06.2008, p. 545-553.

Research output: Contribution to journalArticle

Yanaru-Fujisawa, R, Matsumoto, T, Ushijima, Y, Esaki, M, Hirahashi, M, Gushima, M, Yao, T, Nakabeppu, Y & Iida, M 2008, 'Genomic and functional analyses of MUTYH in Japanese patients with adenomatous polyposis', Clinical Genetics, vol. 73, no. 6, pp. 545-553. https://doi.org/10.1111/j.1399-0004.2008.00998.x
Yanaru-Fujisawa, R. ; Matsumoto, T. ; Ushijima, Y. ; Esaki, M. ; Hirahashi, M. ; Gushima, M. ; Yao, T. ; Nakabeppu, Y. ; Iida, M. / Genomic and functional analyses of MUTYH in Japanese patients with adenomatous polyposis. In: Clinical Genetics. 2008 ; Vol. 73, No. 6. pp. 545-553.
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