Two Unique Mutations in HTRA1-Related Cerebral Small Vessel Disease in North America and Africa and Literature Review

Ty Shang, Marco Pinho, Debarti Ray, Alka Khera

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Objective: To describe and compare two cases of North American and African patients who were diagnosed with HTRA1-related cerebral small vessel disease (CSVD) with homozygous and heterozygous mutations, respectively, in the linker domain of the HTRA1 gene. Materials and methods: Case reports and literature review. Results: A 49-year-old man from Mexico presented with recurrent lacunar strokes and memory loss. A 46-year-old woman from Eritrea presented with progressive memory loss. Neither patient had alopecia. MRI of the brain and spine in both patients showed leukoencephalopathy, microbleeds and spondylosis. Microbleeds along the subpial surfaces of the brainstem were only seen in the Mexican man. Genetic sequencing of HTRA1 gene revealed a novel homozygous mutation of p.A173S in the Mexican man supporting cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). A heterozygous mutation of p.V175M was detected in the African woman, which has not been reported in patients of African ethnicity. In reviewing literature, CARASIL patients with mutation in the linker domain are older at neurological symptom onset and more frequently presented with stroke compared to patients with non-linker domain mutations. In patients of HTRA1-CSVD from heterozygous mutations, male is more common. Conclusions: HTRA1-related CSVD may be seen in patients of non-Asian ethnicity without alopecia. These case reports extend the clinical and radiographic spectrum of HTRA1-related CSVD.

Original languageEnglish (US)
Article number106029
JournalJournal of Stroke and Cerebrovascular Diseases
Issue number11
StatePublished - Nov 2021


  • Cerebrovascular diseases
  • Genetics
  • HTRA1 mutation
  • MRI
  • Stroke
  • Vascular dementia

ASJC Scopus subject areas

  • Surgery
  • Rehabilitation
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine


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