Unusual Clinical Presentations in Subjects Carrying Novel NOTCH3 Gene Mutations

Spinicci, Gabriella; Conti, Maria; Cherchi, Maria Valeria; Mancosu, Cristina; Murru, Raffaele; Carboni, Nicola

doi:10.1016/j.jstrokecerebrovasdis.2013.02.002

Cited by 1 publication

(1 citation statement)

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“…39 A very important manifestation seems to be acute encephalopathy or coma. 40 This is a rather misleading manifestation that has been reproduced several times in the literature but is extremely rare. Acute encephalopathy has been reported in 2 cases as the initial manifestation of the disorder in our reviewed cases.…”

Section: Discussionmentioning

confidence: 94%

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy revisited

et al. 2020

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ObjectiveThe 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.

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Section: Discussionmentioning

confidence: 94%