Open AccessA novel heterozygous HTRA1 mutation in an Asian family with CADASIL‐like disease
Author(s) -
Cao Hua,
Liu Jiahui,
Tian Wen,
Ji Xiaofei,
Wang Qi,
Luan Siyu,
Dong Xiang,
Dong Huijie
Publication year - 2022
Publication title -
journal of clinical laboratory analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 50
eISSN - 1098-2825
pISSN - 0887-8013
DOI - 10.1002/jcla.24174
Subject(s) - cadasil , proband , genetics , missense mutation , exon , sanger sequencing , leukoencephalopathy , locus (genetics) , compound heterozygosity , biology , mutation , exome sequencing , gene , medicine , disease , pathology
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.