caa a22 4500 445808012 CHVBK 20180317145202.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1007/s00415-011-5983-3 doi (NATIONALLICENCE)springer-10.1007/s00415-011-5983-3 First report of a pathogenic mutation on exon 24 of the NOTCH3 gene in a CADASIL family [Elektronische Daten] [Raffaella Valenti, Silvia Bianchi, Francesca Pescini, Camilla D'Eramo, Domenico Inzitari, Maria Dotti, Leonardo Pantoni] Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetically transmitted small vessel disease clinically characterized by migraine, recurrent subcortical strokes, and cognitive and mood disorders. Pathogenic mutations are located on any of the exons of the NOTCH3 gene coding for epidermal-growth factor (EGF)-like repeats of the extracellular domain of the NOTCH3 receptor. Because the gene is large and the mutations cluster on some exons, many laboratories restrict the analysis to these exons. We report the first missense mutation involving exon 24 and causing CADASIL in a 64-year-old man. The patient was admitted to the hospital for a loss of consciousness accompanied by profuse sweating. On examination, some parkinsonian features were present. Over the last 4years, he had developed postural instability and gait disturbances with repeated falls, behavioral disorders, and cognitive impairment. A diagnostic hypothesis of atypical parkinsonism had been advanced. The presence of multiple subcortical lacunar infarcts and leukoencephalopathy extended to the external capsule on cerebral MRI suggested the presence of CADASIL. The diagnosis was confirmed by finding a heterozygous mutation leading to a cysteine substitution on exon 24 of the NOTCH3 gene. One proband's brother, who had progressive gait disturbances, unilateral action tremor and bradykinesia, and an asymptomatic niece also resulted affected. This report underlines that when CADASIL is suspected the genetic analysis should be performed on all the NOTCH3 exons coding for EGF-like repeats including exon 24 and confirms that CADASIL may have heterogeneous phenotypes. Springer-Verlag, 2011 CADASIL nationallicence NOTCH3 nationallicence Phenotype nationallicence Leukoencephalopathy nationallicence Magnetic resonance imaging nationallicence Parkinsonism nationallicence Valenti Raffaella Department of Neurological and Psychiatric Sciences, University of Florence, Largo Brambilla 3, 50134, Florence, Italy aut Bianchi Silvia Department of Neurological and Behavioural Sciences, University of Siena, Siena, Italy aut Pescini Francesca Department of Neurological and Psychiatric Sciences, University of Florence, Largo Brambilla 3, 50134, Florence, Italy aut D'Eramo Camilla Department of Neurological and Behavioural Sciences, University of Siena, Siena, Italy aut Inzitari Domenico Department of Neurological and Psychiatric Sciences, University of Florence, Largo Brambilla 3, 50134, Florence, Italy aut Dotti Maria Department of Neurological and Behavioural Sciences, University of Siena, Siena, Italy aut Pantoni Leonardo Department of Neurological and Psychiatric Sciences, University of Florence, Largo Brambilla 3, 50134, Florence, Italy aut Journal of Neurology Springer-Verlag 258/9(2011-09-01), 1632-1636 0340-5354 258:9<1632 2011 258 415 https://doi.org/10.1007/s00415-011-5983-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00415-011-5983-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Valenti Raffaella Department of Neurological and Psychiatric Sciences, University of Florence, Largo Brambilla 3, 50134, Florence, Italy aut NATIONALLICENCE 700 1- Bianchi Silvia Department of Neurological and Behavioural Sciences, University of Siena, Siena, Italy aut NATIONALLICENCE 700 1- Pescini Francesca Department of Neurological and Psychiatric Sciences, University of Florence, Largo Brambilla 3, 50134, Florence, Italy aut NATIONALLICENCE 700 1- D'Eramo Camilla Department of Neurological and Behavioural Sciences, University of Siena, Siena, Italy aut NATIONALLICENCE 700 1- Inzitari Domenico Department of Neurological and Psychiatric Sciences, University of Florence, Largo Brambilla 3, 50134, Florence, Italy aut NATIONALLICENCE 700 1- Dotti Maria Department of Neurological and Behavioural Sciences, University of Siena, Siena, Italy aut NATIONALLICENCE 700 1- Pantoni Leonardo Department of Neurological and Psychiatric Sciences, University of Florence, Largo Brambilla 3, 50134, Florence, Italy aut NATIONALLICENCE 773 0- Journal of Neurology Springer-Verlag 258/9(2011-09-01), 1632-1636 0340-5354 258:9<1632 2011 258 415 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer