Here, we report brain white matter alterations in individuals clinically and genetically diagnosed with periodontal Ehlers–Danlos syndrome, a rare disease characterized by premature loss of teeth and connective tissue abnormalities. Eight individuals of two families clinically diagnosed with periodontal Ehlers–Danlos syndrome were included in the present study and underwent general physical, dental, and neurological examination. Whole exome sequencing was performed, and all patients included in the study underwent MRI of the brain. Whole exome sequencing revealed heterozygous C1R mutations c.926G>T (p.Cys309Phe, Family A) and c.149_150TC>AT (p.Val50Asp, Family B). All adult individuals (n = 7; age range 31 to 68 years) investigated by MRI had brain white matter abnormalities. The MRI of one investigated child aged 8 years was normal. The MRI pattern was suggestive of an underlying small vessel disease that is progressive with age. As observed in other leukoencephalopathies related to microangiopathies, the extent of the white matter changes was disproportionate to the neurologic features. Medical history revealed recurrent headaches or depression in some cases. Neurological examination was unremarkable in all individuals but one had mild cognitive decline and ataxia and experienced a seizure. The observation that periodontal Ehlers–Danlos syndrome caused by missense mutations in C1R is consistently associated with a leukoencephalopathy opens a new pathogenic link between the classical complement pathway, connective tissue, brain small vessels, and brain white matter abnormalities.

中文翻译：

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牙周埃勒斯-丹洛斯综合征与白质脑病有关。

在这里，我们报告临床和遗传学诊断患有牙周埃勒斯-丹洛斯综合征的个体的脑白质改变，这种罕见疾病以牙齿过早脱落和结缔组织异常为特征。本研究包括临床诊断为牙周埃勒斯-丹洛斯综合征的两个家族的八个人，并对他们进行了常规的身体，牙齿和神经系统检查。进行了完整的外显子组测序，该研究中包括的所有患者均接受了脑部MRI检查。整个外显子组测序显示杂合的C1R突变为c.926G> T（p.Cys309Phe，家族A）和c.149_150TC> AT（p.Val50Asp，家族B）。所有成年个体（n = 7; MRI检查的年龄范围为31至68岁）有脑白质异常。一名接受调查的8岁儿童的MRI正常。MRI模式提示潜在的小血管疾病随着年龄的增长而发展。正如在其他与微血管病变有关的白质脑病中所观察到的，白质变化的程度与神经系统特征不成比例。病史显示某些情况下反复出现头痛或抑郁。神经系统检查在所有个体中均无异常，但其中一个具有轻度的认知下降和共济失调，并发作过。牙周Ehlers-Danlos综合征由C1R的错义突变引起的观察 与白质脑病持续相关的疾病在经典补体途径，结缔组织，脑小血管和脑白质异常之间开启了新的致病联系。