We present a family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and elevated lipoprotein(a) [Lp(a)] levels. In addition to neurological examinations, ultrasound of extra- and intracranial arteries, laboratory tests, and cerebral magnetic resonance imaging (MRI), a whole genome screening with mutation analyses was performed. Rather untypical for CADASIL, stenoses of large intracranial arteries were detected in the index patient. All affected subjects lacked a history of migraine, mood disturbances, and cognitive decline despite extensive white matter lesions in two individuals. Furthermore, evidence of early cerebral microangiopathy was demonstrated in three children (age 9, 11 and 13). We were able to explain the mechanism of elevated Lp(a) on the basis of the kringle IV type 2 repetition size. A mutation S118C located in exon 4 of Notch3 was responsible for CADASIL. Elevated Lp(a) might have contributed to the cerebrovascular phenotype in this family.
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http://dx.doi.org/10.1007/s00415-010-5496-5 | DOI Listing |
J Biol Chem
October 2024
Department of Biochemistry, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Chiba, Japan; Research Institute of Disaster Medicine, Chiba University, Chiba, Chiba, Japan; Health and Disease Omics Center, Chiba University, Chiba, Chiba, Japan. Electronic address:
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic vascular dementia characterized by age-related degeneration of vascular mural cells and accumulation of a NOTCH3 mutant protein. NOTCH3 functions as a signaling receptor, activating downstream gene expression in response to ligands like JAG1 and DLL4, which regulate the development and survival of mural cells. This signal transduction process is thought to be connected with NOTCH3 endocytic degradation.
View Article and Find Full Text PDFFront Neurol
August 2024
Department of Neurosciences, University of California, San Diego, San Diego, CA, United States.
J Clin Med
May 2024
Department of Neurology, Virgen Macarena University Hospital, 41009 Seville, Spain.
: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary small vessel disease leading to significant morbidity and mortality. Despite advances in genetic diagnosis, the underlying pathophysiology remains incompletely understood. Proteomic studies offer insights into disease mechanisms by identifying altered protein expression patterns.
View Article and Find Full Text PDFMicrobiome
September 2023
Department of Neurology, Center for the Study of Mental and Neurological Disorders, the Third Affiliated Hospital of Sun Yat-Sen University, Sun Yat-Sen University, Guangzhou, 510630, Guangdong, China.
Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease that carries mutations in NOTCH3. The clinical manifestations are influenced by genetic and environmental factors that may include gut microbiome.
Results: We investigated the fecal metagenome, fecal metabolome, serum metabolome, neurotransmitters, and cytokines in a cohort of 24 CADASIL patients with 28 healthy household controls.
Eur Heart J Case Rep
September 2023
Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.
Background: Spontaneous coronary artery dissection (SCAD) is increasingly diagnosed as one of the infrequent causes of acute coronary syndrome. Almost no cause was identified in half of the cases. Here, we report a rare case of spontaneous coronary artery dissection with leucoencephalopathy (SCADLE) associated with a mutation of the thrombospondin Type 1 domain containing 1 (THSD1) gene.
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