title: RET mutational spectrum in Hirschsprung disease: evaluation of 601 Chinese patients.
abstract: 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.
authors.affiliation: Department of Surgery, University of Hong Kong, Hong Kong, China.
authors.forename: Man-Ting
authors.initials: MT
authors.lastname: So
authors.forename: Thomas Yuk-Yu
authors.initials: TY
authors.lastname: Leon
authors.forename: Guo
authors.initials: G
authors.lastname: Cheng
authors.forename: Clara Sze-Man
authors.initials: CS
authors.lastname: Tang
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Miao
authors.forename: Belinda K
authors.initials: BK
authors.lastname: Cornes
authors.forename: Ngoc Ngo
authors.initials: NN
authors.lastname: Diem
authors.forename: Long
authors.initials: L
authors.lastname: Cui
authors.forename: Elly Sau-Wai
authors.initials: ES
authors.lastname: Ngan
authors.forename: Vincent Chai-Hang
authors.initials: VC
authors.lastname: Lui
authors.forename: Xuan-Zhao
authors.initials: XZ
authors.lastname: Wu
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Hualong
authors.initials: H
authors.lastname: Wang
authors.forename: Zheng-Wei
authors.initials: ZW
authors.lastname: Yuan
authors.forename: Liu-Ming
authors.initials: LM
authors.lastname: Huang
authors.forename: Long
authors.initials: L
authors.lastname: Li
authors.forename: Huimin
authors.initials: H
authors.lastname: Xia
authors.forename: Deli
authors.initials: D
authors.lastname: Zhu
authors.forename: Juncheng
authors.initials: J
authors.lastname: Liu
authors.forename: Thanh Liem
authors.initials: TL
authors.lastname: Nguyen
authors.forename: Ivy Hau-Yee
authors.initials: IH
authors.lastname: Chan
authors.forename: Patrick Ho-Yu
authors.initials: PH
authors.lastname: Chung
authors.forename: Xue-Lai
authors.initials: XL
authors.lastname: Liu
authors.forename: Ruizhong
authors.initials: R
authors.lastname: Zhang
authors.forename: Kenneth Kak-Yuen
authors.initials: KK
authors.lastname: Wong
authors.forename: Pak-Chung
authors.initials: PC
authors.lastname: Sham
authors.forename: Stacey S
authors.initials: SS
authors.lastname: Cherny
authors.forename: Paul Kwong-Hang
authors.initials: PK
authors.lastname: Tam
authors.forename: Maria-Mercè
authors.initials: MM
authors.lastname: Garcia-Barcelo
mesh_terms: D044466:Asian People / Q000235:genetics*; D002681:China; D005069:Evaluation Studies as Topic; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006627:Hirschsprung Disease / Q000145:classification / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*
chemical_list: D051096:Proto-Oncogene Proteins c-ret