Familial brain arteriovenous malformation maps to 5p13–q14, 15q11–q13 or 18p11: Linkage analysis with clipped fingernail DNA on high-density SNP array

Abstract Familial arteriovenous malformations (AVM) in the brain is a very rare disease. It is defined as its occurrence in two or more relatives (up to third-degree relatives) in a family without any associated disorders, such as hereditary hemorrhagic telangiectasia. We encountered a Japanese fami...

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Bibliographic Details
Published in:European journal of medical genetics 2010-09, Vol.53 (5), p.244-249
Main Authors: Oikawa, Masahiro, Kuniba, Hideo, Kondoh, Tatsuro, Kinoshita, Akira, Nagayasu, Takeshi, Niikawa, Norio, Yoshiura, Koh-ichiro
Format: Article
Language:English
Subjects:
Adolescent
Arteriovenous malformation
Child
Chromosome Mapping
Female
Fingernail DNA
GeneChip
Genetic Predisposition to Disease
Genetic Testing
Genome-Wide Association Study
Genomewide linkage analysis
Haplotypes
Humans
Intracranial Arteriovenous Malformations - genetics
Lod Score
Male
Medical Education
Microsatellite Repeats
Mutation
Mutation search
Pedigree
Polymorphism, Single Nucleotide
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Summary:Abstract Familial arteriovenous malformations (AVM) in the brain is a very rare disease. It is defined as its occurrence in two or more relatives (up to third-degree relatives) in a family without any associated disorders, such as hereditary hemorrhagic telangiectasia. We encountered a Japanese family with brain AVM in which four affected members in four successive generations were observed. One DNA sample extracted from leukocytes of the proband and ten DNA samples from clipped finger nails of other members were available. A genome-wide linkage analysis was performed on this pedigree using Affymetrix GeneCip 10K 2.0 Xba Array and MERLIN software. We obtained sufficient performance of SNP genotyping in the fingernail samples with the mean SNP call rate of 92.49%, and identified 18 regions with positive LOD scores. Haplotype and linkage analyses with microsatellite markers at these regions confirmed three possible disease-responsible regions, i.e., 5p13.2–q14.1, 15q11.2–q13.1 and 18p11.32–p11.22. Sequence analysis was conducted for ten selected candidate genes at 5p13.2–q14.1, such as MAP3K1 , DAB2 , OCLN , FGF10 , ESM1 , ITGA1 , ITGA2 , EGFLAM , ERBB2IP , and PIK3R1 , but no causative genetic alteration was detected. This is the first experience of adoption of fingernail DNA to genome-wide, high-density SNP microarray analysis, showing candidate brain AVM susceptible regions.
ISSN:1769-7212
1878-0849
DOI:10.1016/j.ejmg.2010.06.007