Possible correlation between KRIT1 variant and non-atherosclerotic vasculopathy resulting in ischemic stroke

To provide the first instance of ischemic stroke attributable to vasculopathy linked to a pathogenic variant in the Krev interaction trapped-1 (KRIT1) gene, which has previously been recognized solely for its involvement in cerebral cavernous malformations (CCMs).

A 23-year-old male patient with acute ischemic stroke and a familial history of early-onset stroke underwent evaluation using cerebral angiography, magnetic resonance imaging (MRI), and clinical exome sequencing. A comprehensive pedigree investigation was conducted, uncovering a history of stroke among several family members, so suggesting a potential inherited risk.

The patient demonstrated non-atherosclerotic vasculopathy on cerebral angiography. Genetic investigation identified a heterozygous missense variation, c.1867 C> T (p.Thr623Met), in the KRIT1 gene. The variation was also identified in additional impacted family members.

This case indicates a new correlation between KRIT1 pathogenic mutations and non-atherosclerotic vasculopathy, broadening the phenotypic spectrum of KRIT1-related disease to encompass ischemic stroke absent classic CCM symptoms.