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Scientific article
Open access
English

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, genetic homogeneity, and mapping of the locus within a 2-cM interval

Published inAmerican journal of human genetics, vol. 58, no. 1, p. 171-181
Publication date1996
Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a recently identified autosomal dominant cerebral arteriopathy characterized by the recurrence of subcortical infarcts leading to dementia. A genetic linkage analysis conducted in two large families recently allowed us to map the affected gene on chromosome 19 in a 12-cM interval bracketed by D19S221 and D19S215. In the present study, these first 2 families and 13 additional ones, including a total of 199 potentially informative meiosis, have been genotyped with eight polymorphic markers located between D19S221 and D19S215. All families were linked to chromosome 19. The highest combined lod score (Zmax = 37.24 at theta = .01) was obtained with marker D19S841, a new CAn microsatellite marker that we isolated from chromosome 19 cosmids. The recombinant events observed within these families were used to refine the genetic mapping of CADASIL within a 2-cM interval that is now bracketed by D19S226 and D19S199 on 19p13.1. These data strongly suggest the genetic homogeneity of this recently identified condition and establish the value of its clinical and neuroimaging diagnostic criteria. Besides their importance for the ongoing positional cloning of the CADASIL gene, these data help to refine the genetic mapping of CADASIL relative to familial hemiplegic migraine and hereditary paroxysmal cerebellar ataxia, conditions that we both mapped within the same chromosome 19 region.

Keywords
  • Cerebral Arterial Diseases/genetics
  • Cerebral Infarction/genetics
  • Chromosome Mapping
  • Chromosomes, Human, Pair 19
  • DNA/blood
  • DNA, Satellite/genetics
  • Dementia/genetics
  • Demyelinating Diseases/genetics
  • Europe
  • Female
  • Genes, Dominant
  • Genetic Linkage
  • Genetic Markers
  • Humans
  • Male
  • Pedigree
  • Polymorphism, Genetic
  • Recombination, Genetic
  • Syndrome
Citation (ISO format)
DUCROS, A et al. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, genetic homogeneity, and mapping of the locus within a 2-cM interval. In: American journal of human genetics, 1996, vol. 58, n° 1, p. 171–181.
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Article (Published version)
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ISSN of the journal0002-9297
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