[Identification of a novel NOTCH3 mutation in a family featuring cerebral autosomal dominant arteriopathy with subcortical infarct and leucoencephalopathy].

[cadasil]

To analyze potential mutations of NOTCH 3 gene in a Chinese family featuring cerebral autosomal dominant arteriopathy with subcortical infarct and leucoencephalopathy (CADASIL ) in order to facilitate genetic counseling and prenatal diagnosis .The proband and related family members and 100 healthy controls were recruited . The NOTCH 3 gene was screened for mutations by polymerase chain reaction and direct DNA sequencing . PolyPhen-2 and SIFT software were used to predict the protein function .The proband and two affected individuals from the family were adult-onset , with main clinical manifestations including recurrent transient ischemic attacks and (or ) strokes , cognitive impairment , memory decline , and depression . MRI findings suggested multiple cerebral infarcts and severe leukoencephalopathy . A novel heterozygous missense mutation c .3043 T > A (p .Cys 1015 S er ) located in exon 19 of NOTCH 3 gene was identified not only in the proband and two patients , but also in an asymptomatic relative from the family . The same mutation was detected in none of the 100 unrelated healthy controls . Function analysis suggested that this mutation can severely affect the functions of this protein . Multiple sequence alignment revealed that the mutation site was extremely conserved in various species .A novel heterozygous Cys 1015 S er mutations in exon 19 of the NOTCH 3 gene probably underlies the CADASIL in this family .