MYO5B 基因突变可能会促进极早发炎症性肠病的发生:一份病例报告。

IF 2.1 4区 医学 Q3 GENETICS & HEREDITY
Yue Lou, Yao Lv, Jindan Yu, Weizhong Gu, Ming Jiang, Jie Chen
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引用次数: 0

摘要

背景:随着基因测序技术的不断进步,已有 60 多种与极早发炎性肠病(VEO-IBD)相关的基因突变被报道。其中大多数基因与免疫缺陷有关。肌球蛋白 5B (MYO5B) 基因主要参与细胞运动和物质运输,与先天性难治性腹泻和胆汁淤积症有关。目前还没有研究探讨 MYO5B 基因与 VEO-IBD 之间的关系。我们报告了一例MYO5B基因突变的患儿,该患儿被诊断为VEO-IBD,然后我们研究了MYO5B基因与VEO-IBD之间的关系:一名7个月大的女婴,主诉为 "便血4个多月,阴道脓血分泌物3周",被诊断为VEO-IBD。全外周血进行了全基因组测序。对回肠末端组织进行了免疫组化。用回肠末端培养的类器官组织进行了 Western 印迹、定量聚合酶链反应(Q-PCR)和免疫荧光。全外显子组测序发现了意义不明的 MYO5B 杂合子错义变体(p. [I769N]; [T1546M])。免疫组化显示,MYO5B突变患儿回肠末端的MYO5B蛋白表达量显著下降;Q-PCR显示,患者体内闭塞素和ZO-1的mRNA水平下降,MYO5B的mRNA水平和蛋白水平均下调。免疫荧光图像显示,MYO5B 基因突变破坏了转运体 SGLT1、NHE3 和 AQP7 的顶端输送:结论:MYO5B基因突变导致MYO5B蛋白下调,可能会降低肠道紧密连接基因的mRNA和蛋白水平,使顶端转运体错位,从而促进VEO-IBD的发生。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
MYO5B gene mutations may promote the occurrence of very early onset inflammatory bowel disease: a case report.

Background: With recent advances in gene sequencing technology, more than 60 genetic mutations associated with very early onset inflammatory bowel disease (VEO-IBD) have been reported. Most of the genes are associated with immune deficiencies. The Myosin 5B (MYO5B) gene is primarily involved in cell motility and material transport which is associated with congenital intractable diarrhea and cholestasis. No studies have examined the relationship between the MYO5B gene and VEO-IBD. We report a case of a child with a mutation in the MYO5B gene who was diagnosed with VEO-IBD, then we investigated the association between the MYO5B gene and VEO-IBD.

Case presentation: A 7-month-old baby girl with a chief complaint of "blood in the stool for more than 4 months and vaginal pus and blood discharge for 3 weeks" was diagnosed with VEO-IBD, and her symptoms improved after treatment with mesalazine. The whole-exome sequencing was performed with peripheral blood. Immunohistochemistry was performed on the terminal ileal tissue. Western blotting, quantitative polymerase chain reaction (Q-PCR) and immunofluorescence were performed with cultured organoid tissue from the terminal ileum. Whole-exome sequencing identified heterozygous missense of MYO5B variant of unknown significance (p. [I769N]; [T1546M]). Immunohistochemistry revealed a significant decrease in the expression of MYO5B protein in the terminal ileum of the child with MYO5B mutation; Q-PCR revealed a decrease in the mRNA levels of occludin and ZO-1 and both the mRNA levels and protein levels of MYO5B was downregulated in the patient. Immunofluorescence images showed that MYO5B gene mutation disrupted the apical delivery of transporters SGLT1, NHE3 and AQP7.

Conclusions: MYO5B gene mutation leading to the downregulation of MYO5B protein may promote the occurrence of VEO-IBD by decreasing mRNA and protein levels of intestinal tight junction genes and dislocating the apical transporters.

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来源期刊
BMC Medical Genomics
BMC Medical Genomics 医学-遗传学
CiteScore
3.90
自引率
0.00%
发文量
243
审稿时长
3.5 months
期刊介绍: BMC Medical Genomics is an open access journal publishing original peer-reviewed research articles in all aspects of functional genomics, genome structure, genome-scale population genetics, epigenomics, proteomics, systems analysis, and pharmacogenomics in relation to human health and disease.
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