RET somatic mutations are underrecognized in Hirschsprung disease.
RET somatic mutations are underrecognized in Hirschsprung disease.
复制标题
RET 体细胞突变在先天性巨结肠中的作用未被充分认识
DOI：
10.1038/gim.2017.178
复制
发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Jiang Q;Liu F;Miao C;Li Q;Zhang Z;Xiao P;Su L;Yu K;Chen X;Zhang F;Chakravarti A;Li L
我们的目的是确定赫希斯普朗疾病（HSCR）中RET镶嵌的频率，测试它是否被低估并评估其对HSCR风险的贡献。
进行了靶向外观测序（n = 83）和RET单基因筛选（n = 69）。
我们确定了152例患者（5.2％）的8个从头突变，其中6例是病原体突变。此外，在四个未受影响的儿童的临床受试者中发现了种系镶嵌物（突变等位基因频率：1 - 28％）。
在HSCR中，RET基因的体细胞突变对看似零星突变的患者的父母进行了识别。
Purpose:We aimed to determine the frequency of RET mosaicism in Hirschsprung disease (HSCR), test whether it has been underestimated, and to assess its contribution to HSCR risk.Methods:Targeted exome sequencing (n = 83) and RET single-gene screening (n = 69) were performed. Amplicon-based deep sequencing was applied on multiple tissue samples. TA cloning and sequencing were conducted for validation.Results:We identified eight de novo mutations in 152 patients (5.2%), of which six were pathogenic mosaic mutations. Two of these patients were somatic mosaics, with mutations detected in blood, colon, and saliva (mutant allele frequency: 35-44%). In addition, germ-line mosaicism was identified in four clinically unaffected subjects, each with an affected child, in multiple tissues (mutant allele frequency: 1-28%).Conclusion:Somatic mutations of the RET gene are underrecognized in HSCR. Molecular investigation of the parents of patients with seemingly sporadic mutations is essential to determine recurrence risk in these families.
登录
查看更多内容
影响因子：
2.7
作者：
Schill EM;Lake JI;Tusheva OA;Nagy N;Bery SK;Foster L;Avetisyan M;Johnson SL;Stenson WF;Goldstein AM;Heuckeroth RO
通讯作者：
Heuckeroth RO
通过靶向 SIGLEC-8，miR-215 在先天性巨结肠发病机制中的作用。
影响因子：
--
作者：
Lei, Hao;Li, Hongxing;Tang, Weibing
通讯作者：
Tang, Weibing
影响因子：
12.3
作者：
Gui H;Schriemer D;Cheng WW;Chauhan RK;Antiňolo G;Berrios C;Bleda M;Brooks AS;Brouwer RW;Burns AJ;Cherny SS;Dopazo J;Eggen BJ;Griseri P;Jalloh B;Le TL;Lui VC;Luzón-Toro B;Matera I;Ngan ES;Pelet A;Ruiz-Ferrer M;Sham PC;Shepherd IT;So MT;Sribudiani Y;Tang CS;van den Hout MC;van der Linde HC;van Ham TJ;van IJcken WF;Verheij JB;Amiel J;Borrego S;Ceccherini I;Chakravarti A;Lyonnet S;Tam PK;Garcia-Barceló MM;Hofstra RM
通讯作者：
Hofstra RM
影响因子：
9.8
作者：
Emison, Eileen Sproat;Garcia-Barcelo, Merce;Chakravarti, Aravinda
通讯作者：
Chakravarti, Aravinda
影响因子：
9.8
作者：
Leuer, M;Oldenburg, J;Olek, K
通讯作者：
Olek, K