Abstract
Familial cerebral cavernous malformation type 1 (CCM1) is an autosomal dominant disease caused by mutations in the Krev Interaction Trapped 1 (KRIT1/CCM1) gene, and characterized by brain lesions that can cause hemorrhagic strokes, seizures, and neurological deficits. Carriers of the same genetic mutation can present with variable symptoms and severity of disease, suggesting the influence of modifier factors. Genetic modifiers of CCM1 disease severity have been recently identified and included common genetic variants in inflammatory, immune response, and oxidative stress genes and pathways. Here, we describe the genotyping of CCM1 patients with the same gene mutation (Q455X) using a high-throughput genotyping array optimized for individuals of Hispanic/Latino ancestry. We then review the quality control steps following the genome-wide genotyping. Genome-wide genotyping of larger cohorts of CCM1 patients might reveal additional genetic variants contributing to the disease severity of CCM1.
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Acknowledgments
This work was supported by the Brain Vascular Malformation Consortium (BVMC). The BVMC (U54 NS065705) is part of the NIH Rare Disease Clinical Research Network, supported through a collaboration between the NIH Office of Rare Diseases Research at the National Center for Advancing Translational Science (NCATS) and the National Institute of Neurological Disorders and Stroke (NINDS).
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Choquet, H., Kim, H. (2020). Genome-wide Genotyping of Cerebral Cavernous Malformation Type 1 Individuals to Identify Genetic Modifiers of Disease Severity. In: Trabalzini, L., Finetti, F., Retta, S. (eds) Cerebral Cavernous Malformations (CCM) . Methods in Molecular Biology, vol 2152. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0640-7_6
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DOI: https://doi.org/10.1007/978-1-0716-0640-7_6
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