[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 .

Diseases
Validation

Diseases presenting "prenatal diagnosis" symptom

22q11.2 deletion syndrome

achondroplasia

adrenomyeloneuropathy

alexander disease

alpha-thalassemia

aromatase deficiency

benign recurrent intrahepatic cholestasis

cadasil

canavan disease

classical phenylketonuria

cohen syndrome

congenital adrenal hyperplasia

congenital diaphragmatic hernia

congenital toxoplasmosis

cystinuria

dentinogenesis imperfecta

epidermolysis bullosa simplex

harlequin ichthyosis

holt-oram syndrome

homocystinuria without methylmalonic aciduria

hydrocephalus with stenosis of the aqueduct of sylvius

junctional epidermolysis bullosa

kindler syndrome

krabbe disease

lamellar ichthyosis

megacystis-microcolon-intestinal hypoperistalsis syndrome

monosomy 21

neonatal adrenoleukodystrophy

oculocutaneous albinism

omenn syndrome

phenylketonuria

primary hyperoxaluria type 1

pyruvate dehydrogenase deficiency

severe combined immunodeficiency

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

zellweger syndrome

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