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.2182C>T 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.