Heterozygous HTRA1 missense mutation in CADASIL-like family disease

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebrovascular disease.
• Identifying the genetic basis of CADASIL-like conditions is crucial for diagnosis and treatment.

Purpose of the Study:

• To identify pathogenic genes associated with CADASIL-like disease in a familial cohort.
• To investigate the role of the high temperature requirement protease A1 (HTRA1) gene in hereditary cerebral small vessel disease.

Main Methods:

• Direct sequencing of known hereditary cerebral vascular genes in the proband.
• High-throughput multiplex polymerase chain reaction (PCR) for single nucleotide polymorphism (SNP) analysis in family members.
• Clinical and imaging data collection for familial cases.

Main Results:

• A missense mutation in the high temperature requirement protease A1 (HTRA1) gene was identified in the proband.
• Biological software analysis suggested the HTRA1 mutation as a potential pathogenic factor.
• SNP analysis confirmed the HTRA1 gene mutation in other affected family members.

Conclusions:

• The CADASIL-like disease in this family is likely caused by a heterozygous HTRA1 gene mutation.
• This mutation leads to autosomal dominant hereditary cerebral small vessel disease.
• HTRA1 is implicated as a pathogenic gene in CADASIL-like conditions.