A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
TREX1 p.A129fs and p.Y305C variants in a large multi-ethnic cohort of CADASIL-like unrelated patients
Tekijät: Foddis M, Blumenau S, Holtgrewe M, Paquette K, Westra K, Alonso I, Macario MD, Morgadinho AS, Velon AG, Santo G, Santana I, Mönkäre S, Kuuluvainen L, Schleutker J, Pöyhönen M, Myllykangas L, Pavlovic A, Kostic V, Dobricic V, Lohmann E, Hanagasi H, Santos M, Guven G, Bilgic B, Bras J, Beule D, Dirnagl U, Guerreiro R, Sassi C
Kustantaja: ELSEVIER SCIENCE INC
Julkaisuvuosi: 2023
Lehti:: Neurobiology of Aging
Tietokannassa oleva lehden nimi: NEUROBIOLOGY OF AGING
Lehden akronyymi: NEUROBIOL AGING
Vuosikerta: 123
Aloitussivu: 208
Lopetussivu: 215
Sivujen määrä: 8
ISSN: 0197-4580
DOI: https://doi.org/10.1016/j.neurobiolaging.2022.11.013
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and retinal vasculopathy with cerebral leukodystrophy and systemic manifestations (RVCL-S) are the most common forms of rare monogenic early-onset cerebral small vessel disease and share clinical, and, to different extents, neuroradiological and neuropathological features. However, whether CADASIL and RVCL-S overlapping phenotype may be explained by shared genetic risk or causative factors such as TREX1 coding variants remains poorly understood. To investigate this intriguing hypothesis, we used exome sequencing to screen TREX1 protein-coding variability in a large multi-ethnic cohort of 180 early-onset independent familial and apparently sporadic CADASIL-like Caucasian patients from the USA, Portugal, Finland, Serbia and Turkey. We report 2 very rare and likely pathogenic TREX1 mutations: a loss of function mutation (p.Ala129fs) clustering in the catalytic domain, in an apparently sporadic 46-year-old patient from the USA and a missense mutation (p.Tyr305Cys) in the well conserved C-terminal region, in a 57-year-old patient with positive family history from Serbia. In concert with recent findings, our study expands the clinical spectrum of diseases associated with TREX1 mutations. (c) 2022 Elsevier Inc. All rights reserved.
