title: Novel Mutation of the NOTCH3 Gene in a Chinese Pedigree with CADASIL.
abstract: BACKGROUND
  Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) results from NOTCH3 gene mutations, which lead to the degeneration of vascular smooth muscle cells (VSMCs). The clinical presentation of CADASIL patients is dependent on the impact of other vascular risk factors and the type of NOTCH3 mutation present.
  
  
  METHODS
  Here, we report a rare pathogenic mutation on exon 14 of the NOTCH3 gene in a Chinese family affected by CADASIL with phenotypic peculiarities. We performed genetic testing, clinical and neuropsychological examination, brain magnetic resonance images (MRI), and electron microscopy (EM) in skin biopsies.
  
  
  RESULTS
  NOTCH3 gene analysis revealed a c.2182CT substitution on exon 14, which is the first example of this mutation in a Chinese individual from the Han ancestry. Granular osmiophilic material (GOM) was found in the proband, and all patients had migraine, subcortical ischemic events, and mood disturbances, without progressive cognitive impairment. Cranial MRI further showed white matter hyperintensity, involving bilateral basal ganglia and multiple microbleeds (MBs), in the thalamus and brain stem.
  
  
  CONCLUSIONS
  This study suggests that different missense mutations in NOTCH3 might contribute to atypical clinical features of CADASIL. This report also indicates that for individuals with a positive family history having clinical and neuroradiological findings suggestive of CADASIL, genetic testing and GOM detection should be performed.
authors: Xiaoxia
authors: X
authors: Hou
authors: Chuan
authors: C
authors: He
authors: Qingwen
authors: Q
authors: Jin
authors: Qi
authors: Q
authors: Niu
authors: Guang
authors: G
authors: Ren
authors: Department of Neurology, First Affiliated Hospital of Nanjing Medical University, P.O. Box: No. 300, Guangzhou Road, Nanjing 210029, Jiangsu Province,. China.
authors: Hong
authors: H
authors: Cheng
mesh_terms: D000368:Aged; D019943:Amino Acid Substitution; D044466:Asian People; D001479:Basal Ganglia / Q000473:pathology; D046589:CADASIL / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D005091:Exons / Q000235:genetics; D005820:Genetic Testing; D006470:Hemorrhage / Q000235:genetics / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics; D009483:Neuropsychological Tests; D010375:Pedigree; D000071656:Receptor, Notch3 / Q000235:genetics*; D012867:Skin / Q000473:pathology; D066127:White Matter / Q000473:pathology
chemical_list: C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3
keywords: CADASIL; NOTCH3 gene.; genetic testing; ischemic infarction; microbleeds; migraine