ArticleNeurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology2015
TREX1 C-terminal frameshift mutations in the systemic variant of retinal vasculopathy with cerebral leukodystrophy.
Article in Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25 citing papers in PubMed, 60 citations in OpenAlex.
- First case ofFrontiers in immunology · 2026Article
- Understanding Headaches Attributed to Cranial and/or Cervical Vascular Disorders: Insights and Challenges for Neurologists.Pain and therapy · 2024Review
- Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations in conjunction with systemic lupus erythematosus: Missed diagnosis or misdiagnosis?Immunity, inflammation and disease · 2024Article
- The Dawn and Advancement of the Knowledge of the Genetics of Migraine.Journal of clinical medicine · 2024Review
- TREX1 cytosolic DNA degradation correlates with autoimmune disease and cancer immunity.Clinical and experimental immunology · 2023Article
- Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic manifestations (RVCL-S): An update on basic science and clinical perspectives.Cerebral circulation - cognition and behavior · 2022Article
- Heritable and non-heritable uncommon causes of stroke.Journal of neurology · 2021Review
- High clinical heterogeneity in a Chinese pedigree of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S).Orphanet journal of rare diseases · 2021Article
- A rare case of occlusive juxtafoveolar retinal telangiectasias associated with lesions of the central nervous system: A cerebroretinal vasculopathy like phenotype without mutations in the TREX1 gene.American journal of ophthalmology case reports · 2020Article
- Migraine and rare neurological disorders.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2020Review
- TREX1 - Apex predator of cytosolic DNA metabolism.DNA repair · 2020Article
- TGF-β Signaling: A Therapeutic Target to Reinstate Regenerative Plasticity in Vascular Dementia?Aging and disease · 2020Review
- How common are single gene mutations as a cause for lacunar stroke? A targeted gene panel study.Neurology · 2019Article
- Mechanistic link between DNA damage sensing, repairing and signaling factors and immune signaling.Advances in protein chemistry and structural biology · 2019Review
- TREX1 is expressed by microglia in normal human brain and increases in regions affected by ischemia.Brain pathology (Zurich, Switzerland) · 2018Article
- Monogenic Lupus: A Developing Paradigm of Disease.Frontiers in immunology · 2018Review
- A Loss-of-FunctionFrontiers in molecular neuroscience · 2018Article
- Genetics of vascular dementia - review from the ICVD working group.BMC medicine · 2017Review
- Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations.Brain : a journal of neurology · 2016Article
- Retinal vasculitis.Current opinion in rheumatology · 2016Review
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Retinal vasculopathy with cerebral leukodystrophy (RVCL) is an adult-onset disorder caused by C-terminal heterozygous frameshift (fs) mutations in the human 3'-5' DNA exonuclease TREX1. Hereditary systemic angiopathy (HSA) is considered a variant of RVCL with systemic involvement of unknown genetic cause, described in a unique family so far. Here we describe the second case of RVCL with systemic involvement, characterized by cerebral calcifications and pseudotumoral lesions, retinopathy, osteonecrosis, renal and hepatic failure. The genetic screening of TREX1 in this patient revealed the novel heterozygous T270fs mutation on the C-terminal region. On the same gene, we found the V235fs mutation, formerly shown in RVCL, in one patient previously reported with HSA. These mutations lead to important alterations of the C-terminal of the protein, with the loss of the transmembrane helix (T270fs) and the insertion of a premature stop codon, resulting in a truncated protein (V235fs). Functional analysis of T270fs-mutated fibroblasts showed a prevalent localization of the protein in the cytosol, rather than in the perinuclear region. RVCL with systemic involvement is an extremely rare condition, whose diagnosis is complex due to multiorgan manifestations, unusual radiological and histopathological findings, not easily attributable to a single disease. It should be suspected in young adults with systemic microangiopathy involving retina, liver, kidney, bones and brain. Here we confirm the causative role played by TREX1 autosomal dominant fs mutations disrupting the C-terminal of the protein, providing a model for the study of stroke in young adults.
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