Author:
Castro Madelyn,Venkateswaran Nisha,Peters Samuel T.,Deyle David R.,Bower Matthew,Koob Michael D.,Boeve Bradley F.,Vossel Keith
Abstract
Frontotemporal dementia (FTD) rarely occurs in individuals under the age of 30, and genetic causes of early-onset FTD are largely unknown. The current report follows a 27 year-old patient with no significant past medical history presenting with two years of progressive changes in behavior, rushed speech, verbal aggression, and social withdrawal. MRI and FDG-PET imaging of the brain revealed changes maximally in the frontal and temporal lobes, which along with the clinical features, are consistent with behavioral variant FTD. Next generation sequencing of a panel of 28 genes associated with dementia and amyotrophic lateral sclerosis (ALS) initially revealed a duplication of exon 15 inMatrin-3(MATR3). Whole genome sequencing determined that this genetic anomaly was, in fact, a sequence corresponding with full-lengthMATR3variant 5 inserted into chromosome 12, indicating retrotransposition from a messenger RNA intermediate. To our knowledge, this is a novel mutation ofMATR3, as the majority of mutations inMATR3linked to FTD-ALS are point mutations. Genomic DNA analysis revealed that this mutation is also present in one unaffected first-degree relative and one unaffected second-degree relative. This suggests that the mutation is either a disease-causing mutation with incomplete penetrance, which has been observed in heritable FTD, or a benign variant. Retrotransposons are not often implicated in neurodegenerative diseases; thus, it is crucial to clarify the potential role of thisMATR3variant 5 retrotransposition in early-onset FTD.
Subject
Neurology (clinical),Neurology
Cited by
5 articles.
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