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NEJM：先天性巨结肠病分子遗传解剖学与风险分析

2019-04-11 MedSci MedSci原创

分子遗传解剖学先天性巨结肠病肠神经嵴细胞
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研究发现，先天性巨结肠病起源于常见的非编码变异、罕见的编码变异和影响肠神经嵴细胞发育相关基因的拷贝数变异，不同基因型特异性风险差异67倍

先天性巨结肠是一种发育性肠道神经系统疾病，是新生儿和婴儿肠梗阻最常见的原因。该疾病的遗传风险超过80%，包括与肠神经系统相关基因中罕见和常见的序列变异以及单基因和染色体综合征。

近日研人员对190名先天性巨结肠患者样本进行基因分型和外显子测序，先前的研究认为DNA序列变异、大拷贝数变异和核型变异是致病性的，与先天性巨结肠病或其他神经发育障碍显著相关。

本次研究新确定了4个非编码元件中存在5个或5个以上与先天性巨结肠发病风险相关的变异体（患者vs对照组，48.4% vs 17.1%）。24个与肠神经嵴细胞发育相关的罕见基因编码变异中，7个是新发现的（患者vs对照组，34.7% vs 5.0%），并且与非编码变体相比，患者风险显著（OR=10.02）。罕见的大拷贝数变异（患者vs对照组，11.4% vs 0.2%）患者的疾病风险最高（OR=63.07）。在72.1%的患者中发现至少一个可识别的遗传危险因子，至少48.4%的患者在编码受体酪氨酸激酶(RET)的基因中存在结构或调节缺陷。不同变异人群的先天性巨结肠风险为1/18800至1/120。

研究发现，先天性巨结肠病起源于常见的非编码变异、罕见的编码变异和影响肠神经嵴细胞发育相关基因的拷贝数变异，不同基因型特异性风险差异67倍。

原始出处：

Joseph M. Tilghman et al. Molecular Genetic Anatomy and Risk Profile of Hirschsprung's Disease.N Engl J Med， April 11，2019.

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    2019-04-13 huirong

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    2019-04-13 751943081_32627954

    #先天性巨结肠#

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    2019-04-13 654699882_84926992

    #解剖学#

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    2019-04-11 旺医

    顶刊就是顶刊，谢谢梅斯带来这么高水平的研究报道，我们科里同事经常看梅斯，分享梅斯上的信息

    0