Familial cerebral small vessel disease inclusion criteria • Clinical features consistent with cerebral small vessel disease: either lacunar stroke or vascular cognitive impairment/dementia, AND • MRI confirmed evidence of cerebral small vessel disease as evidenced by; multiple lacunar infarcts and/or confluent white matter hyperintensities, AND • Early onset cerebral SVD (<60 years) without cardiovascular risk factors or affected first degree family member Individuals with severe or syndromic disease should be recruited according to standard guidance, typically as trios. Disease status of apparently unaffected participants should be determined according to standard clinical practice to detect cryptic disease. In other cases, unaffected individuals should not be recruited. Recruitment in such families should favour multiplex families over single isolated cases. These singleton recruits will not contribute to the overall singleton monitoring metrics applied to GMCs. Familial cerebral small vessel disease exclusion criteria • Causes of white matter disease other than cerebral small vessel disease (e.g. multiple sclerosis, vasculitis, leukodystrophy). • Cases with NOTCH3 mutations Prior genetic testing guidance - Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition. - Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing. PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out. Familial cerebral small vessel disease prior genetic testing genes Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: NOTCH3 Closing statement These requirements will be kept under continual review during the main programme and may be subject to change.
Ellen McDonagh (Genomics England Curator)
Group: Other
Workplace: Other
Caroline Wright (Genomics England Curator)
Group: Other
Workplace: Genomics England
Sarah Leigh (Genomics England Curator)
Group: Other
Workplace: Other
Rhea Tan (University of Cambridge)
Group: GeCIP domain
Workplace: Research lab
Louise Daugherty (Genomics England Curator)
Group: Other
Workplace: Other
Eleanor Williams (Genomics England Curator)
Group: Other
Workplace: Other
Zornitza Stark (Australian Genomics)
Group: Other
Workplace: Other clinical service
Ivone Leong (Genomics England Curator)
Group: Other
Workplace: Other
| List | Entity | Reviews | Mode of inheritance | Details | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Green List (high evidence) |
ABCC6 |
2 reviews1 green |
BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
APP |
2 reviews1 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
ATP1A2 |
2 reviews1 red |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
CACNA1A |
2 reviews1 red |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
COL3A1 |
3 reviews1 green |
BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
COL4A1 |
2 reviews1 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
COL4A2 |
2 reviews1 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
COLGALT1 |
2 reviews1 green |
BIALLELIC, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
FOXC1 |
3 reviews1 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
GLA |
2 reviews1 green |
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
HTRA1 |
2 reviews1 green |
BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
NOTCH3 |
4 reviews1 green |
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown |
Sources
Phenotypes
Tags |
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| Green List (high evidence) |
TREX1 |
2 reviews1 green |
BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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| Red List (low evidence) |
CST3 |
3 reviews1 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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| Red List (low evidence) |
FOXF2 |
1 review1 red |
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown |
Sources
Phenotypes
Tags |
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| Red List (low evidence) |
ITM2B |
2 reviews1 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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| Red List (low evidence) |
SCN1A |
2 reviews1 red |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Promoted to version 1. 4th July 2016