High-temperature requirement A serine peptidase 1 gene-related autosomal dominant cerebral small vessel disease: clinical and genetic characteristics
10.3760/cma.j.cn113694-20240425-00297
- VernacularTitle:HTRA丝氨酸肽酶1基因相关显性遗传脑小血管病的临床表型及遗传学分析
- Author:
Xiaoyu CHEN
1
;
Yun TIAN
;
Hong WANG
;
Wenping GU
;
Fang YI
Author Information
1. 中南大学湘雅医院神经外科，长沙 410008
- Keywords:
Cerebral small vessel disease;
High-temperature requirement A serine peptidase 1;
Mutation
- From:
Chinese Journal of Neurology
2024;57(8):874-880
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the clinical phenotype and genetic characteristics of cerebral small vessel disease (CSVD) caused by heterozygous mutations in high-temperature requirement A serine peptidase 1 ( HTRA1) gene. Methods:Nine patients with HTRA1 gene related autosomal dominant CSVD diagnosed in the Departments of Geriatrics and Neurology,Xiangya Hospital of Central South University between January 2020 and December 2023 were selected. Their clinical data were collected, and the probands received genetic test using whole exome sequencing. The mutations were then verified in the family using Sanger sequencing, and their clinical and genetic characteristics were summarized. Results:Among the 9 patients with HTRA1 gene related autosomal dominant CSVD, the onset age was (51.1±9.5) years. Cognitive impairment, stroke onset, and gait disturbance were the most common clinical manifestations. Magnetic resonance imaging examination usually revealed diffuse white matter lesions, multiple lacunar cerebral infarction, multiple cerebral microbleeds, and brain atrophy, which were consistent with the radiological characteristics of CSVD. Most patients showed a decrease in Aβ42 levels and Aβ42/Aβ40 ratio in cerebrospinal fluid, and 2/4 of patients had an increase in phosphory protein tau levels. Seven heterozygous mutations in the HTRA1 gene were found in 9 patients, including two new heterozygous missense mutations, c.1160T>C(p.M387T) and c.569G>T(p. A190L). Conclusions:The clinical manifestations of HTRA1 gene-related autosomal dominant CSVD patients are mainly cognitive impairment, stroke and gait disturbance, and the imaging features are consistent with CVSD changes. HTRA1 gene c.1160T>C(p.M387T) and c.569G>T(p.A190L) heterozygous missense mutations are newly reported mutations, expanding the genetic mutation spectrum of this disease.
