RET mutational spectrum in Hirschsprung disease: evaluation of 601 Chinese patients.
Rare (RVs) and common variants of the RET gene contribute to Hirschsprung disease (HSCR; congenital aganglionosis). While RET common variants are strongly associated with the commonest manifestation of the disease (males; short-segment aganglionosis; sporadic), rare coding sequence (CDS) variants ar...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3235168?pdf=render |
| _version_ | 1818677316691165184 |
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| author | Man-Ting So Thomas Yuk-Yu Leon Guo Cheng Clara Sze-Man Tang Xiao-Ping Miao Belinda K Cornes Ngoc Ngo Diem Long Cui Elly Sau-Wai Ngan Vincent Chai-Hang Lui Xuan-Zhao Wu Bin Wang Hualong Wang Zheng-Wei Yuan Liu-Ming Huang Long Li Huimin Xia Deli Zhu Juncheng Liu Thanh Liem Nguyen Ivy Hau-Yee Chan Patrick Ho-Yu Chung Xue-Lai Liu Ruizhong Zhang Kenneth Kak-Yuen Wong Pak-Chung Sham Stacey S Cherny Paul Kwong-Hang Tam Maria-Mercè Garcia-Barcelo |
| author_facet | Man-Ting So Thomas Yuk-Yu Leon Guo Cheng Clara Sze-Man Tang Xiao-Ping Miao Belinda K Cornes Ngoc Ngo Diem Long Cui Elly Sau-Wai Ngan Vincent Chai-Hang Lui Xuan-Zhao Wu Bin Wang Hualong Wang Zheng-Wei Yuan Liu-Ming Huang Long Li Huimin Xia Deli Zhu Juncheng Liu Thanh Liem Nguyen Ivy Hau-Yee Chan Patrick Ho-Yu Chung Xue-Lai Liu Ruizhong Zhang Kenneth Kak-Yuen Wong Pak-Chung Sham Stacey S Cherny Paul Kwong-Hang Tam Maria-Mercè Garcia-Barcelo |
| author_sort | Man-Ting So |
| collection | DOAJ |
| description | Rare (RVs) and common variants of the RET gene contribute to Hirschsprung disease (HSCR; congenital aganglionosis). While RET common variants are strongly associated with the commonest manifestation of the disease (males; short-segment aganglionosis; sporadic), rare coding sequence (CDS) variants are more frequently found in the lesser common and more severe forms of the disease (females; long/total colonic aganglionosis; familial).Here we present the screening for RVs in the RET CDS and intron/exon boundaries of 601 Chinese HSCR patients, the largest number of patients ever reported. We identified 61 different heterozygous RVs (50 novel) distributed among 100 patients (16.64%). Those include 14 silent, 29 missense, 5 nonsense, 4 frame-shifts, and one in-frame amino-acid deletion in the CDS, two splice-site deletions, 4 nucleotide substitutions and a 22-bp deletion in the intron/exon boundaries and 1 single-nucleotide substitution in the 5' untranslated region. Exonic variants were mainly clustered in RET the extracellular domain. RET RVs were more frequent among patients with the most severe phenotype (24% vs. 15% in short-HSCR). Phasing RVs with the RET HSCR-associated haplotype suggests that RVs do not underlie the undisputable association of RET common variants with HSCR. None of the variants were found in 250 Chinese controls. |
| first_indexed | 2024-12-17T08:57:26Z |
| format | Article |
| id | doaj.art-2bc637cd25a94f7abcae0723d404adea |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T08:57:26Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2bc637cd25a94f7abcae0723d404adea2022-12-21T21:55:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01612e2898610.1371/journal.pone.0028986RET mutational spectrum in Hirschsprung disease: evaluation of 601 Chinese patients.Man-Ting SoThomas Yuk-Yu LeonGuo ChengClara Sze-Man TangXiao-Ping MiaoBelinda K CornesNgoc Ngo DiemLong CuiElly Sau-Wai NganVincent Chai-Hang LuiXuan-Zhao WuBin WangHualong WangZheng-Wei YuanLiu-Ming HuangLong LiHuimin XiaDeli ZhuJuncheng LiuThanh Liem NguyenIvy Hau-Yee ChanPatrick Ho-Yu ChungXue-Lai LiuRuizhong ZhangKenneth Kak-Yuen WongPak-Chung ShamStacey S ChernyPaul Kwong-Hang TamMaria-Mercè Garcia-BarceloRare (RVs) and common variants of the RET gene contribute to Hirschsprung disease (HSCR; congenital aganglionosis). While RET common variants are strongly associated with the commonest manifestation of the disease (males; short-segment aganglionosis; sporadic), rare coding sequence (CDS) variants are more frequently found in the lesser common and more severe forms of the disease (females; long/total colonic aganglionosis; familial).Here we present the screening for RVs in the RET CDS and intron/exon boundaries of 601 Chinese HSCR patients, the largest number of patients ever reported. We identified 61 different heterozygous RVs (50 novel) distributed among 100 patients (16.64%). Those include 14 silent, 29 missense, 5 nonsense, 4 frame-shifts, and one in-frame amino-acid deletion in the CDS, two splice-site deletions, 4 nucleotide substitutions and a 22-bp deletion in the intron/exon boundaries and 1 single-nucleotide substitution in the 5' untranslated region. Exonic variants were mainly clustered in RET the extracellular domain. RET RVs were more frequent among patients with the most severe phenotype (24% vs. 15% in short-HSCR). Phasing RVs with the RET HSCR-associated haplotype suggests that RVs do not underlie the undisputable association of RET common variants with HSCR. None of the variants were found in 250 Chinese controls.http://europepmc.org/articles/PMC3235168?pdf=render |
| spellingShingle | Man-Ting So Thomas Yuk-Yu Leon Guo Cheng Clara Sze-Man Tang Xiao-Ping Miao Belinda K Cornes Ngoc Ngo Diem Long Cui Elly Sau-Wai Ngan Vincent Chai-Hang Lui Xuan-Zhao Wu Bin Wang Hualong Wang Zheng-Wei Yuan Liu-Ming Huang Long Li Huimin Xia Deli Zhu Juncheng Liu Thanh Liem Nguyen Ivy Hau-Yee Chan Patrick Ho-Yu Chung Xue-Lai Liu Ruizhong Zhang Kenneth Kak-Yuen Wong Pak-Chung Sham Stacey S Cherny Paul Kwong-Hang Tam Maria-Mercè Garcia-Barcelo RET mutational spectrum in Hirschsprung disease: evaluation of 601 Chinese patients. PLoS ONE |
| title | RET mutational spectrum in Hirschsprung disease: evaluation of 601 Chinese patients. |
| title_full | RET mutational spectrum in Hirschsprung disease: evaluation of 601 Chinese patients. |
| title_fullStr | RET mutational spectrum in Hirschsprung disease: evaluation of 601 Chinese patients. |
| title_full_unstemmed | RET mutational spectrum in Hirschsprung disease: evaluation of 601 Chinese patients. |
| title_short | RET mutational spectrum in Hirschsprung disease: evaluation of 601 Chinese patients. |
| title_sort | ret mutational spectrum in hirschsprung disease evaluation of 601 chinese patients |
| url | http://europepmc.org/articles/PMC3235168?pdf=render |
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