Previous work has suggested that those with mutations in EGFrs 1-6 may have more severe clinical presentations than those with mutations in EGFr 7-34. (see here for our EGFr guidance). This study tries to further understand the risks associated with mutations in each EGFr domain.
The researchers determined three groups: High-risk, medium-risk and low-risk, based on how common a mutation in any given EGFr domain was in CADASIL cohorts compared to the population studies (e.g. Biobank). If the mutation was frequent in CADASIL cohorts and not so frequent in general population studies, it was considered high-risk and vice versa. Using these groupings the authors found that those with high-risk mutations were at highest risk of stroke, followed by medium and then low-risk mutations. Similar patterns were observed for MRI features too. This study provides a step forward in being able to better predict CADASIL prognosis in individuals.
Reference:
Hack RJ, Gravesteijn G, Cerfontaine MN, Santcroos MA, Gatti L, Kopczak A, Bersano A, Duering M, Rutten JW, Lesnik Oberstein SAJ. Three-tiered EGFr domain risk stratification for individualized NOTCH3-small vessel disease prediction. Brain. 2023 Jul 3;146(7):2913-2927. doi: 10.1093/brain/awac486. PMID: 36535904; PMCID: PMC10316769. Click here for PubMed abstract.