AUTHOR=Li Yu-Ming , Jia Wei , Xin Tao , Fang Yu-Qing
TITLE=Case report: Heterozygous mutation in HTRA1 causing typical cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy
JOURNAL=Frontiers in Genetics
VOLUME=14
YEAR=2023
URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1235650
DOI=10.3389/fgene.2023.1235650
ISSN=1664-8021
ABSTRACT=Background: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is an autosomal recessive disorder characterized by baldness, recurrent ischemic stroke, lumbago, headache, and dementia which is closely related to homozygous mutations of the high-temperature requirement serine peptidase A1 (HTRA1) gene. Heterozygous mutations of HTRA1 are usually considered to be non-pathogenic. Although it has been revealed that only a few patients with heterozygous mutations could present some manifestations, their clinical symptoms were atypical, milder, and always with a lower frequency of extra-neurological features. Here, a rare patient with heterozygous mutation of HTRA1 who had all typical features of CARASIL as well as severe clinical symptoms and rapid progression was initially reported in our study.
Case presentation: A 43-year-old female patient presented with a gradual onset of headache and cognitive decline. As time progressed, her headache intensified and symptoms of dementia began to manifest gradually. During her early years, she had thinning hair and subsequently experienced two occurrences of ischemic strokes in her thirties. Furthermore, she also had a history of lumbago and urinary retention before visiting our hospital. The patient’s magnetic resonance imaging revealed the presence of widespread white matter lesions, infarctions, and microbleeds, in addition to lumbar disc herniation and degenerative lesions. The observed clinical characteristics had a strong correlation with CARASIL, and the patient was diagnosed with a heterozygous missense mutation of 905G>A (Arg302Gln) in the HTRA1 gene. The patient has been under continuous follow-up for a duration exceeding 3 years subsequent to her release from the hospital. She underwent cystostomy, and symptoms of bulbar paralysis developed in a progressive way. Currently, there has been a notable decrease in motor function and activities of daily living, resulting in the individual being confined to bed for a duration exceeding 1 year.
Conclusion: This case suggests that patients carrying a heterozygous mutation in G905A may also have typical clinical features of CARASIL, which allows us to have a more comprehensive understanding of CARASIL.