Clinical and genetic features in a family with CADASIL and high lipoprotein (a) values.
We present a family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and elevated lipoprotein(a) [Lp(a)] levels. In addition to neurological examinations, ultrasound of extra- and intracranial arteries, laboratory tests, and cerebral magnetic resonance imaging (MRI), a whole genome screening with mutation analyses was performed. Rather untypical for CADASIL, stenoses of large intracranial arteries were detected in the index patient. All affected subjects lacked a history of migraine, mood disturbances, and cognitive decline despite extensive white matter lesions in two individuals. Furthermore, evidence of early cerebral microangiopathy was demonstrated in three children (age 9, 11 and 13). We were able to explain the mechanism of elevated Lp(a) on the basis of the kringle IV type 2 repetition size. A mutation S118C located in exon 4 of Notch3 was responsible for CADASIL. Elevated Lp(a) might have contributed to the cerebrovascular phenotype in this family.
Gong
Maolian
M
Max-Delbrück-Center for Molecular Medicine (MDC), Berlin, Germany.
Rueschendorf
Franz
F
Marx
Peter
P
Schulz
Herbert
H
Kraft
Hans-Georg
HG
Huebner
Norbert
N
Koennecke
Hans-Christian
HC
D000293:Adolescent; D000328:Adult; D000368:Aged; D046589:CADASIL / Q000097:blood / Q000235:genetics*; D002536:Cerebral Arteries / Q000000981:diagnostic imaging / Q000473:pathology*; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D020521:Stroke / Q000097:blood / Q000235:genetics; D014463:Ultrasonography
D017270:Lipoprotein(a)