Τίτλος:
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy revisited: Genotype-phenotype correlations of all published cases
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Objective The aim of this study was to evaluate the correlation between the various NOTCH3 mutations and their clinical and genetic profile, along with the presentation of a novel mutation in a patient.MethodsHere, we describe the phenotype of a patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) harboring a novel mutation. We also performed an extensive literature research for NOTCH3 mutations published since the identification of the gene and performed a systematic review of all published cases with NOTCH3 mutations. We evaluated the mutation pathogenicity in a great number of patients with detailed clinical and genetic evaluation and investigated the possible phenotype-genotype correlations.ResultsOur patient harbored a novel mutation in the NOTCH3 gene, the c.3084 G > C, corresponding to the aminoacidic substitution p.Trp1028Cys, presenting with seizures as the first neurologic manifestation. We managed to find a correlation between the pathogenicity of mutations, severity of the phenotype, and age at onset of CADASIL. Significant differences were also identified between men and women regarding the phenotype severity.ConclusionsThe collection and analysis of these scarce data published since the identification of NOTCH3 qualitatively by means of a systematic review and quantitatively regarding genetic profile and pathogenicity scores, highlight the significance of the ongoing trend of investigating phenotypic genotypic correlations. © 2020 American Academy of Neurology.
Συγγραφείς:
Xiromerisiou, G.
Marogianni, C.
Dadouli, K.
Zompola, C.
Georgouli, D.
Provatas, A.
Theodorou, A.
Zervas, P.
Nikolaidou, C.
Stergiou, S.
Ntellas, P.
Sokratous, M.
Stathis, P.
Paraskevas, G.P.
Bonakis, A.
Voumvourakis, K.
Hadjichristodoulou, C.
Hadjigeorgiou, G.M.
Tsivgoulis, G.
Περιοδικό:
Neurology: Genetics
Εκδότης:
Lippincott Williams and Wilkins
Λέξεις-κλειδιά:
atorvastatin; clopidogrel; escitalopram; genomic DNA; levetiracetam; Notch3 receptor, adult; asymptomatic disease; autoimmune disease; brain angiography; brain hemorrhage; brother; CADASIL; case report; cerebrospinal fluid analysis; cerebrovascular accident; chronic tension headache; clinical article; Cochrane Library; cognitive defect; cognitive flexibility; daughter; depression; disease assessment; disease duration; epilepsy; Fabry disease; family history; father; female; frontal assessment battery; gene mutation; genetic profile; genetic screening; genotype phenotype correlation; Greece; hemiparesis; Holter monitoring; hospital admission; human; human tissue; lacunar stroke; magnetic resonance angiography; male; Medline; middle aged; middle cerebral artery; Mini Mental State Examination; neuroimaging; nuclear magnetic resonance imaging; onset age; outpatient department; personality disorder; phenotype; priority journal; repeat procedure; Review; secondary prevention; skin biopsy; son; susceptibility weighted imaging; systematic review; tertiary care center; tonic clonic seizure; transesophageal echocardiography; traumatic epilepsy; treatment duration; unconsciousness; white matter
DOI:
10.1212/NXG.0000000000000434
