Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy revisited: Genotype-phenotype correlations of all published cases
Data
2020Language
en
Soggetto
Abstract
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.
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Thrift A.G., Tobe-Gai R., Topor-Madry R., Torre A., Tortajada M., Towbin J.A., Tran B.X., Troeger C., Truelsen T., Tsoi D., Tuzcu E.M., Tyrovolas S., Ukwaja K.N., Undurraga E.A., Updike R., Uthman O.A., Uzochukwu B.S.C., Van Boven J.F.M., Vasankari T., Venketasubramanian N., Violante F.S., Vlassov V.V., Vollset S.E., Vos T., Wakayo T., Wallin M.T., Wang Y.-P., Weiderpass E., Weintraub R.G., Weiss D.J., Werdecker A., Westerman R., Whetter B., Whiteford H.A., Wijeratne T., Wiysonge C.S., Woldeyes B.G., Wolfe C.D.A., Woodbrook R., Workicho A., Xavier D., Xiao Q., Xu G., Yaghoubi M., Yakob B., Yano Y., Yaseri M., Yimam H.H., Yonemoto N., Yoon S.-J., Yotebieng M., Younis M.Z., Zaidi Z., El Sayed Zaki M., Zegeye E.A., Zenebe Z.M., Zerfu T.A., Zhang A.L., Zhang X., Zipkin B., Zodpey S., Lopez A.D., Murray C.J.L., GBD 2016 Causes of Death Collaborators (2017)Background: Monitoring levels and trends in premature mortality is crucial to understanding how societies can address prominent sources 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Milicevic M.M., Sarmiento-Suarez R., Sartorius B., Satpathy M., Savic M., Sawhney M., Saylan M.I., Schöttker B., Schutte A.E., Schwebel D.C., Seedat S., Seid A.M., Seifu C.N., Sepanlou S.G., Serdar B., Servan-Mori E.E., Setegn T., Shackelford K.A., Shaheen A., Shahraz S., Shaikh M.A., Shakh-Nazarova M., Shamsipour M., Shariful Islam S.M., Sharma J., Sharma R., She J., Sheikhbahaei S., Shen J., Shi P., Shigematsu M., Shin M.-J., Shiri R., Shoman H., Shrime M.G., Sibamo E.L.S., Sigfusdottir I.D., Silva D.A.S., Silveira D.G.A., Sindi S., Singh A., Singh J.A., Singh O.P., Singh P.K., Singh V., Sinke A.H., Sinshaw A.E., Skirbekk V., Sliwa K., Smith A., Sobngwi E., Soneji S., Soriano J.B., Sousa T.C.M., Sposato L.A., Sreeramareddy C.T., Stathopoulou V., Steel N., Steiner C., Steinke S., Stokes M.A., Stranges S., Strong M., Stroumpoulis K., Sturua L., Sufiyan M.B., Suliankatchi R.A., Sun J., Sur P., Swaminathan S., Sykes B.L., Tabarés-Seisdedos R., Tabb K.M., Taffere G.R., Talongwa R.T., Tarajia M., Tavakkoli M., Taveira N., Teeple S., Tegegne T.K., Tehrani-Banihashemi A., Tekelab T., Tekle D.Y., Temam Shifa G., Terkawi A.S., Tesema A.G., Thakur J.S., Thomson A.J., Tillmann T., Tiruye T.Y., Tobe-Gai R., Tonelli M., Topor-Madry R., Tortajada M., Troeger C., Truelsen T., Tura A.K., Uchendu U.S., Ukwaja K.N., Undurraga E.A., Uneke C.J., Uthman O.A., Van Boven J.F.M., Van Dingenen R., Varughese S., Vasankari T., Venketasubramanian N., Violante F.S., Vladimirov S.K., Vlassov V.V., Vollset S.E., Vos T., Wagner J.A., Wakayo T., Waller S.G., Walson J.L., Wang H., Wang Y.-P., Watkins D.A., Weiderpass E., Weintraub R.G., Wen C.-P., Werdecker A., Wesana J., Westerman R., Whiteford H.A., Wilkinson J.D., Wiysonge C.S., Woldeyes B.G., Wolfe C.D.A., Won S., Workicho A., Workie S.B., Wubshet M., Xavier D., Xu G., Yadav A.K., Yaghoubi M., Yakob B., Yan L.L., Yano Y., Yaseri M., Yimam H.H., Yip P., Yonemoto N., Yoon S.-J., Younis M.Z., Yu C., Zaidi Z., El Sayed Zaki M., Zambrana-Torrelio C., Zapata T., Zenebe Z.M., Zodpey S., Zoeckler L., Zuhlke L.J., Murray C.J.L., GBD 2015 Healthcare Access and Quality Collaborators (2017)Background National levels of personal health-care access and quality can be approximated by measuring mortality rates from causes that should not be fatal in the presence of effective medical care (ie, amenable mortality). ... -
SARS-CoV-2 pathophysiology and its clinical implications: An integrative overview of the pharmacotherapeutic management of COVID-19
Tsatsakis A., Calina D., Falzone L., Petrakis D., Mitrut R., Siokas V., Pennisi M., Lanza G., Libra M., Doukas S.G., Doukas P.G., Kavali L., Bukhari A., Gadiparthi C., Vageli D.P., Kofteridis D.P., Spandidos D.A., Paoliello M.M.B., Aschner M., Docea A.O. (2020)Common manifestations of COVID-19 are respiratory and can extend from mild symptoms to severe acute respiratory distress. The severity of the illness can also extend from mild disease to life-threatening acute respiratory ...