A rare mutation in exon 7 of the NOTCH3 gene in a Chinese CADASIL family: Case report with a literature review

More than 300 mutations have been reported since NOTCH3 was identified as the causal gene of CADASIL. However, mutation sites on exon 7 have rarely been reported in patients with CADASIL. We reported a 44-year-old female from a Chinese family with a clear family history presented with progressive dizziness and gait disturbance for more than 2 months and aggravated for 20 days. Whole- exome sequencing (WES) was used to identify a rare heterozygous missense variant (NM_000435.3: c.1136G>C) of NOTCH3 in this patient. PolyPhen-2 and VarSite predicted that this mutation site was probably pathogenic with the highest score of 1.00 and highly conserved among species. Our case report first identified a rare C379S mutation in exon 7 of NOTCH3 in a Chinese CADASIL family, expanding the ethnic spectrum of this condition. Moreover, in view of our report and literature, if patients have a clear family history and manifest uncommon clinical manifestations of CADASIL such as dizziness and atypical headache, clinicians could consider screening NOTCH3.