Objective

To describe and compare two cases of North American and African patients who were diagnosed with HTRA1-related cerebral small vessel disease (CSVD) with homozygous and heterozygous mutations, respectively, in the linker domain of the HTRA1 gene.

Materials and methods

Case reports and literature review.

Results

A 49-year-old man from Mexico presented with recurrent lacunar strokes and memory loss. A 46-year-old woman from Eritrea presented with progressive memory loss. Neither patient had alopecia. MRI of the brain and spine in both patients showed leukoencephalopathy, microbleeds and spondylosis. Microbleeds along the subpial surfaces of the brainstem were only seen in the Mexican man. Genetic sequencing of HTRA1 gene revealed a novel homozygous mutation of p.A173S in the Mexican man supporting cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). A heterozygous mutation of p.V175M was detected in the African woman, which has not been reported in patients of African ethnicity. In reviewing literature, CARASIL patients with mutation in the linker domain are older at neurological symptom onset and more frequently presented with stroke compared to patients with non-linker domain mutations. In patients of HTRA1-CSVD from heterozygous mutations, male is more common.

Conclusions

HTRA1-related CSVD may be seen in patients of non-Asian ethnicity without alopecia. These case reports extend the clinical and radiographic spectrum of HTRA1-related CSVD.

中文翻译：

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北美和非洲 HTRA1 相关脑小血管病的两个独特突变及文献综述

客观的

描述和比较两例诊断为HTRA1相关脑小血管病 (CSVD)的北美和非洲患者，分别在HTRA1基因的接头域中具有纯合子和杂合子突变。

材料和方法

病例报告和文献综述。

结果

一名来自墨西哥的 49 岁男性因复发性腔隙性中风和记忆力减退就诊。一名来自厄立特里亚的 46 岁妇女出现进行性记忆丧失。两名患者都没有脱发。两名患者的脑部和脊柱 MRI 均显示白质脑病、微出血和脊椎病。沿脑干软膜下表面的微出血仅见于墨西哥男子。HTRA1基因测序基因揭示了一个新的 p.A173S 纯合突变，该突变支持伴有皮层下梗塞和白质脑病 (CARASIL) 的常染色体隐性脑动脉病的墨西哥男子。在非洲女性中检测到 p.V175M 的杂合突变，这在非洲种族患者中尚未见报道。在回顾文献时，与非连接域突变的患者相比，具有连接域突变的 CARASIL 患者在神经系统症状发作时年龄更大，并且更常出现中风。在来自杂合突变的HTRA1- CSVD患者中，男性更常见。

结论

HTRA1相关的 CSVD 可见于非亚洲种族的无脱发患者。这些病例报告扩展了HTRA1相关 CSVD的临床和影像学范围。