Background

Increasing number of mutations responsible for vascular lesions, leading to ischemic or hemorrhagic stroke in young adults, has been identified in the recent years. It has been demonstrated in both mice and humans, that mutations in COL4A1 gene promote cerebral hemorrhages. In humans, both adults and children may be affected, and the spectrum has been broadened recently to neonates and fetuses.

Methods

We present a cohort of eight COL4A1 mutated fetuses in which cerebral hemorrhages were detected by ultrasound leading to elective terminations of pregnancy.

Results

Our neuropathological studies demonstrated a strikingly similar pathological pattern, dominated by supra- and infratentorial multifocal hemorrhagic lesions of various abundance and age in the vicinity of enlarged small vessels having a discontinuous wall. This was constantly associated with a spectrum of supratentorial post-ischemic damages of the grey and white matters. Morphometric studies of brain vessels confirmed vascular dilation and hypervascularization in both grey and white matters and severe attenuation of the smooth-muscle actin staining in the white matter.

Conclusion

These observations add to the rare human neuropathological phenotype of COL4A1 mutations. Its recognition is mandatory to enhance the number of tested patients in the future, as well as the genetic counseling of parents.

中文翻译：

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八例 COL4A1 突变的产前诊断：神经组织病理学表型的进一步描述

背景

近年来，已经发现越来越多的突变导致血管病变，导致年轻人缺血性或出血性中风。已经在小鼠和人类中证明，COL4A1基因的突变会促进脑出血。在人类中，成人和儿童都可能受到影响，最近范围已扩大到新生儿和胎儿。

方法

我们提出了一组 8 个COL4A1突变胎儿，其中通过超声检测到脑出血导致选择性终止妊娠。

结果

我们的神经病理学研究证明了一种惊人相似的病理模式，主要是在具有不连续壁的扩大的小血管附近具有各种丰度和年龄的幕上和幕下多灶性出血性病变。这一直与灰质和白质的一系列幕上缺血后损伤有关。脑血管的形态学研究证实了灰质和白质中的血管扩张和血管过度形成以及白质中平滑肌肌动蛋白染色的严重衰减。

结论

这些观察结果增加了COL4A1突变的罕见人类神经病理学表型。它的认可是强制性的，以增加未来检测患者的数量，以及父母的遗传咨询。