Abstract:

Objective: Two cases of autosomal dominant cerebral small vessel disease caused by HTRA1 gene heterozygous mutation were reported. The clinical phenotypes and imaging features of the disease were summarized via literature review. Methods and Results: Two patients with autosomal dominant cerebral small vessel disease caused by HTRA1 gene heterozygous mutation were diagnosed and treated in The Affiliated Hospital of Guizhou Medical University from November 2023 to February 2025. One patient was a 64-year-old male who developed alopecia at the age of 40 and suffered intracerebral hemorrhage at 52 years old. He subsequently experienced recurrent ischemic strokes complicated by cognitive dysfunction and gait abnormalities. MRI showed diffuse white matter hyperintensities, multiple lacunar infarcts and multiple cerebral microbleeds. Genetic sequencing showed a c.404C > A (p.Ala135Asp) heterozygous mutation in the HTRA1 gene. One patient was a 57-year-old female with memory impairment and abnormal gait as initial manifestations. MRI showed multiple white matter hyperintensities and cerebral microbleeds. Genetic sequencing showed a c.905G > A (p.Arg302Gln) heterozygous mutation in the HTRA1 gene, and her son carried the same mutation. The clinical phenotypes of the two patients were heterogeneous, suggesting that gender and age at onset may affect clinical manifestations. Conclusions: Autosomal dominant cerebral small vessel disease caused by HTRA1 gene heterozygous mutation manifests two distinct clinical phenotypes associated with age and gender. Both patients exhibited characteristic diffuse white matter hyperintensities and multiple cerebral microbleeds. The two cases in this study further broaden the clinical phenotypic spectrum of autosomal dominant cerebral small vessel disease caused by HTRA1 gene heterozygous mutation.

Key words: Cerebral small vessel diseases, High-temperature requirement A serine peptidase 1, Genes, dominant, Mutation, Cognition disorders

摘要：

目的: 报告2例HTRA1基因杂合突变致常染色体显性遗传性脑小血管病病例，通过文献复习，总结疾病临床表型和影像学特征。方法与结果: 贵州医科大学附属医院神经内科2023年11月至2025年2月诊断与治疗2例HTRA1基因杂合突变致常染色体显性遗传性脑小血管病患者。1例为64岁男性，40岁出现秃发，52岁突发脑出血，此后反复缺血性卒中，合并认知功能障碍、步态异常，MRI显示弥漫性脑白质高信号、多发腔隙性梗死及脑微出血灶，基因检测显示存在HTRA1基因c.404C > A（p.Ala135Asp）杂合突变；1例为57岁女性，55岁发病，以记忆力减退、步态异常为主要症状，MRI显示多发脑白质高信号及微出血灶，基因检测显示存在HTRA1基因c.905G > A（p.Arg302Gln）杂合突变，其子携带该突变基因。2例患者临床表型存在异质性，提示性别和发病年龄可能影响临床特征。结论: HTRA1基因杂合突变致常染色体显性遗传性脑小血管病存在性别和年龄差异化临床表型，2例患者均可见特征性弥漫性脑白质高信号、多发脑微出血改变。本文病例进一步拓展了HTRA1基因杂合突变致常染色体显性遗传性脑小血管病的临床表型谱和基因谱。

关键词: 大脑小血管疾病, HtrA丝氨酸肽酶1, 基因，显性, 突变, 认知障碍

CLC Number: 

• R741