To report a novel HTRA1 gene mutation and summarize the clinical phenotypes and genetic characteristics of the family with this heterozygous HTRA1 mutation associated with autosomal dominant cerebral small vessel disease (CSVD).

Clinical data of the proband and his family members were collected. The mutation loci were captured by high-throughput sequencing and validated by Sanger sequencing, and the pathogenicity was predicted by in silico tools. The literature was reviewed.

The proband was a 51-year-old male whose clinical manifestations included sudden numbness of left limbs and cognitive impairment at the age of 50, without typical symptoms of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) such as alopecia and spondylosis. Brain MRI revealed right basal ganglia infarction, symmetric lesions in white matter, and microbleeds. Genetic testing revealed a heterozygous missense mutation of HTRA1 gene (c.941T＞G). Function prediction suggested pathogenicity. His mother suffered from cerebral infarction in her sixties, which resulted in cognitive impairment, and died at the age of 70. His brother carries the same heterozygous mutation, and he suffered from cerebral infarction at the age of 32, resulting in right hemiplegia, speech disorder, and cognitive impairment. His neuroimaging findings were consistent with the imaging features of CSVD. His son carried the same heterozygous mutation but is currently asymptomatic, possibly due to his age.

HTRA1 c. 941T＞G (p.M314R) heterozygous variant is pathogenic, and its clinical phenotype and genetic characteristics are similar to those of HTRA1 gene heterozygous mutation associated autosomal dominant cerebral small vascular disease previously reported.