A Novel NOTCH3 Gene Mutation in a Polish CADASIL Family

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a genetically determined disease of the cerebral vessels, characterized by recurrent ischemic strokes, dementia, and degeneration of the cerebral white matter. The condition is caused by a mutation in the NOTCH3 gene, whose product plays a great role in the development and physiology of the cardiovascular system. Magnetic resonance imaging reveals multiple hyperintensive lesions of the white matter in the T2-weighted images also in asymptomatic carriers of CADASIL and can be detected even 10-15 years prior to clinical signs. Diagnosis is confirmed by genetic testing. We present 2 patients (mother and daughter) carrying the same mutation p.Cys212Gly in 1 allele of the NOTCH-3 gene, which has not yet been recorded in the Human Gene Mutation Database for that gene and therefore described as a new one. The clinical manifestation of the disease differs between patients -the 63-year-old mother has been suffering from severe migraine headaches since her early youth and the first vascular event occurred when she was about 50 years old, she is now presenting with impaired cognitive functions, left facial palsy, bilateral pyramidal syndrome more prominent on the left side, and four-wheel support assisted walking. The neurological deficits that her 42-year-old daughter is afflicted with are discreet. Observation to date indicates a definitely less severe clinical course of the disease. This indicates that members of the same family carrying the same mutation may produce different clinical course of the disease.