Capillary Malformation–Arteriovenous Malformation, a New Clinical and Genetic Disorder Caused by RASA1 Mutations

Eerola, Iiro; Boon, Laurence M.; Mulliken, John B.; Burrows, Patricia E.; Dompmartin, Anne; Watanabe, Shôji; Vanwijck, Romain; Vikkula, Miikka

doi:10.1086/379793

Cited by 637 publications

(526 citation statements)

References 48 publications

(52 reference statements)

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“…The three regions do not overlap with a previously reported candidate locus of familial brain AVM, i.e. 6p25 [17], and do not contain genes responsible for syndromic AVM (heritable disorders involving AVM) or cerebral cavernous malformations, such as ENG [6], ALK1 [7], RASA1 [8][9][10][11][12], and PTEN [13], KRIT1 [14], MGC407 [15], PDCD10 [16].…”

Section: Discussionmentioning

confidence: 87%

“…The proband did not have any mutations in the coding exons or intron/exon boundaries of either gene, nor any genomic aberrations at those loci. We also analyzed RASA1 because this may cause CM-AVM, which is characteraized by multiple CM and AVM [8][9][10][11][12]. No causative mutation or genomic aberration was detected in the proband.…”

Section: Discussionmentioning

confidence: 99%

“…Although several causative genes have been elucidated in some heritable syndromic AVM [6][7][8][9][10][11][12][13][14][15][16], molecular genetic studies of familial or sporadic AVM remain scant.…”

Section: Introductionmentioning

confidence: 99%

“…Mutations in RASA1 at 5q14.3 cause capillary malformation-arteriovenous malformation (CM-AVM) [8][9][10][11][12] characterized by small, round-to-oval, pink-red and multiple CM:…”

Section: Introductionmentioning

confidence: 99%

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

Oikawa

Kuniba

Kondoh³

et al. 2010

European Journal of Medical Genetics

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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.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Mutations in RASA1 at 5q14.3 cause capillary malformation-arteriovenous malformation (CM-AVM) [8][9][10][11][12] characterized by small, round-to-oval, pink-red and multiple CM:…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Oikawa

Kuniba

Kondoh³

et al. 2010

European Journal of Medical Genetics

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“…19 Patient 2 also displays RASA1 deletion. Loss of function mutations in this gene, which is also expressed in brain, are related to capillary and arteriovenous malformation 30 and deletion of this gene may underlie her philtral haemangioma (Figure 1g). …”

Section: Discussionmentioning

confidence: 99%

A novel microdeletion syndrome involving 5q14.3-q15: clinical and molecular cytogenetic characterization of three patients

et al. 2009

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Molecular karyotyping is being increasingly applied to delineate novel disease causing microaberrations and related syndromes in patients with mental retardation of unknown aetiology. We report on three unrelated patients with overlapping de novo interstitial microdeletions involving 5q14.3-q15. All three patients presented with severe psychomotor retardation, epilepsy or febrile seizures, muscular hypotonia and variable brain and minor anomalies. Molecular karyotyping revealed three overlapping microdeletions measuring 5.7, 3.9 and 3.6 Mb, respectively. The microdeletions were identified using single nucleotide polymorphism (SNP) arrays (Affymetrix 100K and Illumina 550K) and array comparative genomic hybridization (1 Mb Sanger array-CGH). Confirmation and segregation studies were performed using fluorescence in situ hybridization (FISH) and quantitative PCR. All three aberrations were confirmed and proven to have occurred de novo. The boundaries and sizes of the deletions in the three patients were different, but an overlapping region of around 1.6 Mb in 5q14.3 was defined. It included five genes: CETN3, AC093510.2, POLR3G, LYSMD3 and the proximal part of GPR98/MASS1, a known epilepsy gene. Haploinsufficiency of GPR98/MASS1 is probably responsible for the seizure phenotype in our patients. At least one other gene contained in the commonly deleted region, LYSMD3, shows a high level of central nervous expression during embryogenesis and is also, therefore, a good candidate gene for other central nervous system (CNS) symptoms, such as psychomotor retardation, brain anomalies and muscular hypotonia of the 5q14.3 microdeletion syndrome.

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Multifocal Capillary Malformations Due to RASA1 Mutation Misdiagnosed as Cutaneous Mastocytosis

Buhl¹,

Shoukier²,

Grzmil³

et al. 2012

Arch Dermatol

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Capillary Malformation–Arteriovenous Malformation, a New Clinical and Genetic Disorder Caused by RASA1 Mutations

Cited by 637 publications

References 48 publications

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

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

A novel microdeletion syndrome involving 5q14.3-q15: clinical and molecular cytogenetic characterization of three patients

Multifocal Capillary Malformations Due to RASA1 Mutation Misdiagnosed as Cutaneous Mastocytosis

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