A novel heterozygous HTRA1 mutation in an Asian family with CADASIL-like disease

Abstract

Background: HTRA1 gene mutations are related to the pathogenesis of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). However, heterozygous HTRA1 mutations at specific sites can also lead to rare autosomal dominant cerebral artery disease (CADASIL-like disease). To date, 28 heterozygous mutations in the HTRA1 gene have been reported to be related to CADASIL-like diseases. Only one case of this disease was caused by a heterozygous mutation of c.497G>T in exon 2 of the HTRA1 gene.

Methods: In this case, we report on an Asian family with CADASIL-like disease caused by a heterozygous mutation of c.497G>T in exon 2 of the HTRA1 gene. The clinical and imaging characteristics of the proband were summarized, and gene mutations were verified by whole-exome sequencing (WES) and direct Sanger sequencing.

Results: The result of the gene sequencing showed a heterozygous missense mutation at the c.497G>T locus of the HTRA1 gene in the proband of one sick family member, resulting in a change in amino acid (p.arg166leu).

Conclusion: This is the first reported pathogenic mutation at the c.497G>T locus of the HTRA1 gene in an Asian population. It provides an important theoretical basis for the specific gene-based diagnosis and treatment of CADASIL-like diseases.

Keywords: HTRA1; CADASIL-like disease; heterozygous mutation.