title: Multi-organ investigation in 16 CADASIL families from central Italy sharing the same R1006C mutation.
abstract: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) may involve many target organs with relevant variability among affected individuals. We performed a multi-organ assessment tapping nervous system, skeletal muscle and cardiovascular system in thirty-nine individuals belonging to 16 families from Central Italy sharing the same R1006C CADASIL mutation. Stroke prevalence was larger in female patients (66.7%) than in males (23.8%); high levels of CKemia were quite frequent (21.6%) and were related to a myopathy without mitochondrial alterations; several individuals had atrial septal aneurysm (10.3%). No specific relationships between common cardiovascular risk factors and clinical manifestations were found. The present systematic study thus identified several gender-related, myopathic and cardiovascular peculiarities of R1006C mutation. This kind of comprehensive approach is necessary to define clinical course, prognosis and treatment options for a multi-organ disease such as CADASIL.
authors.affiliation: Division of Neurology, Mazzoni Hospital, Ascoli Piceno, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Ragno
authors.forename: Luigi
authors.initials: L
authors.lastname: Pianese
authors.forename: Gabriella
authors.initials: G
authors.lastname: Cacchiò
authors.forename: Antonio
authors.initials: A
authors.lastname: Manca
authors.forename: Maria
authors.initials: M
authors.lastname: Scarcella
authors.forename: Serena
authors.initials: S
authors.lastname: Silvestri
authors.forename: Fabio
authors.initials: F
authors.lastname: Di Marzio
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Caiazzo
authors.forename: Flavia
authors.initials: F
authors.lastname: Silvaggio
authors.forename: Giorgio
authors.initials: G
authors.lastname: Tasca
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Mirabella
authors.forename: Luigi
authors.initials: L
authors.lastname: Trojano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000235:genetics*; D046589:CADASIL / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D018376:Cardiovascular Abnormalities / Q000209:etiology; D002784:Cholesterol / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood; D003545:Cysteine / Q000235:genetics*; D018450:Disease Progression; D004576:Electromyography; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007558:Italy; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D009431:Neural Conduction; D009482:Neurophysiology; D009483:Neuropsychological Tests; D010641:Phenotype; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics*; D014057:Tomography, X-Ray Computed
chemical_list: C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D001120:Arginine; D002784:Cholesterol; D003402:Creatine Kinase; D003545:Cysteine