中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (1): 101-102.doi: 10.4103/1673-5374.314296

• 观点:退行性病与再生 • 上一篇    下一篇

印迹基因在小儿散发性脑动静脉畸形中的作用

  

  • 出版日期:2022-01-05 发布日期:2021-09-18

Investigating the role of imprinted genes in pediatric sporadic brain arteriovenous malformations

Concetta Scimone, Luigi Donato*, Antonina Sidoti   

  1. Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, Messina, Italy
  • Online:2022-01-05 Published:2021-09-18
  • Contact: Luigi Donato, PhD, ldonato@unime.it.

摘要: Neural Regen Res:印迹基因损伤可能导致儿童散发性大脑动静脉畸形
     动静脉畸形(AVM)是一种血管先天性缺陷,会影响大脑和周围器官的微脉管系统。而大脑动静脉畸形(bAVM)的发病率为15/100,000,并且无性别区别。bAVM通常出现在成年期。然而,bAVM的严重程度在儿童中有所增加。儿童bAVM约占所有bAVM的3%,通常是偶发的,很少以常染色体显性遗传为特征。散发性儿童bAVM病变被认为是先天性的,可能由胚胎血管形成过程中的缺陷引起。
来自意大利墨西拿大学的Luigi Donato团队首先关注是bAVM可能出现的基因干扰突变。然而在调控序列中发现了一些突变体,如5’-非翻译区和3’-非翻译区。因此,基于印迹机制的复杂性以及表型谱的可变性,Donato团队假设散发性儿童bAVM可能是由于印迹基因的损伤而引起的。而这确实可以解释这种疾病的常染色体显性模式——尽管其父母健康,但受影响的儿童仍表现出这种模式。

文章在《中国神经再生研究(英文版)》杂志2022年1月1期发表。

https://orcid.org/0000-0002-5292-426X (Luigi Donato)

Abstract: Arteriovenous malformation (AVM) is a vascular congenital defect affecting microvasculature of both brain and peripheral organs. Arteriovenous malformation of the brain (bAVM, OMIM #108010), in particular, affects up to 15 per 100,000 persons with no sex predominance. Almost 50% of the patients manifest intracerebral hemorrhage and epileptic seizures, as main clinical symptoms. Anatomically, lesions exhibit the direct shunt from arterioles to venules, lacking the normal capillary bed. Arterioles and venules are curled forming a tangle called nidus. At the nidus, pericytes are reduced. Feeding arteries and draining veins show impaired expression of vessel differentiation markers. These features result in loss of endothelial cells properties and increased permeability of the affected vessels. The high pressure of blood perfusing from arteries to the nidus increases risk of lesion rupture, resulting in intracerebral hemorrhage. Moreover, at the nidus, arterial and venous blood mixes, altering the normal oxygenation of the central nervous system (Barbosa Do Prado et al., 2019).