Xiromerisiou Georgia, Marogianni Chrysoula, Dadouli Katerina, Zompola Christina, Georgouli Despoina, Provatas Antonios, Theodorou Aikaterini, Zervas Paschalis, Nikolaidou Christina, Stergiou Stergios, Ntellas Panagiotis, Sokratous Maria, Stathis Pantelis, Paraskevas Georgios P, Bonakis Anastasios, Voumvourakis Konstantinos, Hadjichristodoulou Christos, Hadjigeorgiou Georgios M, Tsivgoulis Georgios
Department of Neurology (G.X., C.M., D.G., A.P., M.S., G.M.H.), University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece; Second Department of Neurology (C.Z., A.T., P.Z., A.B., K.V., G.T.), "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece; Department of Neurology (G.M.H.), Medical School, University of Cyprus, Nicosia, Cyprus; Department of Hygiene and Epidemiology (K.D., C.H.), Faculty of Medicine, University of Thessaly, Larissa, Greece; Department of Medical Oncology (P.N.), University Hospital of Ioannina, Ioannina, Greece; Department of Neurology (P.S.), Mediterraneo Hospital, Glyfada, Athens, Greece; Histopathological Department (C.N., S.S.), Hippokration General Hospital Thessaloniki; and Department of Neurology (G.P.P.), School of Medicine, National and Kapodistrian University of Athens, Eginition Hospital, Athens, Greece.
Neurol Genet. 2020 May 11;6(3):e434. doi: 10.1212/NXG.0000000000000434. eCollection 2020 Jun.
The aim of this study was to evaluate the correlation between the various mutations and their clinical and genetic profile, along with the presentation of a novel mutation in a patient.
Here, 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 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.
Our patient harbored a novel mutation in the 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.
The collection and analysis of these scarce data published since the identification of 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.
本研究旨在评估各种突变与其临床和基因特征之间的相关性，并展示一名患者的新型突变。
在此，我们描述了一名患有携带新型突变的伴有皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病（CADASIL）患者的表型。我们还对该基因鉴定后发表的突变进行了广泛的文献研究，并对所有已发表的NOTCH3突变病例进行了系统综述。我们通过详细的临床和基因评估，在大量患者中评估了突变的致病性，并研究了可能的表型-基因型相关性。
我们的患者在该基因中存在一种新型突变，即c.3084 G > C，对应于氨基酸替换p.Trp1028Cys，首发神经症状为癫痫发作。我们发现突变的致病性、表型严重程度与CADASIL发病年龄之间存在相关性。在表型严重程度方面，男性和女性之间也存在显著差异。
自该基因鉴定以来发表的这些稀缺数据，通过系统综述在质量上以及在基因特征和致病性评分方面在数量上进行收集和分析，突出了正在进行的研究表型-基因型相关性趋势的重要性。
