ClinVar

In 2 unrelated CADASIL1 (125310) patients, Joutel et al. (1996, 1997) observed a CGC-to-TGC transition in a different codon in exon N3 of the NOTCH3 gene that resulted in substitution of cys for arg (R182C) in the same EGF-like domain.

Joutel et al. (2000) reported a patient who was thought to have CADASIL, although no first-degree relative was affected. The patient was found to carry a heterozygous arg182-to-cys mutation in the NOTCH3 gene; the mutation was absent in his parents, indicating a de novo mutation. They suggested that because of the occurrence of such cases, CADASIL may be more frequent than recognized. The frequency of the condition as a familial disorder is reflected in the fact that Joutel et al. (2000) found that more than 400 families had been identified since 1993. The patient with the arg182-to-cys mutation was a 55-year-old businessman who had experienced recurrent transient focal neurologic episodes, some suggestive of transient ischemic attacks and others of migrainous auras, dating back to the age of 32 years. At 48 years of age, he had a minor ischemic stroke with left facial asymmetry and weakness. Brain MRI showed extensive white matter abnormalities. Multiple sclerosis was suspected. At 53 years, he experienced a pure motor right-sided hemiplegia, which progressed over 5 days. Recovery was only partial, and the patient remained disabled with difficulties in walking and in moving his right hand.