Brain channelopathy eligibility statement: Brain channelopathy inclusion criteria (29579) - Episodic disorder that often causes a combination of ataxia with walking problems, abnormal extra movements, stiff legs, weakness, headache and nausea. - Episodes lasting a few minutes or hours. - There may be a dystonic component and some patients are exhausted for many hours afterwards. - Attacks are not always the same, even with the same genetic defect. - Arms can be affected like legs - Migraine type headaches are frequently associated as is dysarthria - Some patients have a primary headache in the form of hemiplegic migraine (FHM), cluster headache, SUNCT or SUNA - MRI brain and cord to exclude common causes such as tumours, discs, demyelinating causes - Family history of often present in AD or AR forms, X linked pattern rare - Often drugs such as Lamotrigine or acetazolamide are effective 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. Brain channelopathy exclusion criteria (29579) Prior genetic testing guidance (29579) - 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. Brain channelopathy prior genetic testing genes (29579) Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: - KCNA1, PRRT2 as appropriate - CACNA1A (only in dominant, long duration episodic ataxia) Closing statement (29579) 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
Arianna Tucci (Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square)
Group: Other
Workplace: Other
Sarah Leigh (Genomics England Curator)
Group: Other
Workplace: Other
Louise Daugherty (Genomics England Curator)
Group: Other
Workplace: Other
Arianna Tucci (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
Arina Puzriakova (Genomics England Curator)
Group: Other
Workplace: Other
List | Entity | Reviews | Mode of inheritance | Details | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Green List (high evidence) |
ADCY5 |
2 reviews1 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
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Green List (high evidence) |
ATN1_CAGSTR |
3 reviews1 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
ATP1A2 |
3 reviews1 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
ATP1A3 |
3 reviews1 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
ATP7B |
1 review1 green |
BIALLELIC, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
CACNA1A |
4 reviews1 green 1 red |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
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Green List (high evidence) |
CACNA1A_CAGSTR |
2 reviews |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
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Green List (high evidence) |
CACNB4 |
3 reviews1 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
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Green List (high evidence) |
CSTB_CCCCGCCCCGCGSTR |
2 reviews |
BIALLELIC, autosomal or pseudoautosomal |
Sources
Phenotypes
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Green List (high evidence) |
GLRA1 |
1 review1 green |
BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
Sources
Phenotypes
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Green List (high evidence) |
GLRB |
1 review1 green |
BIALLELIC, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
Xp11.23 region (includes MAOA and MAOB) LossISCA-37468-LossRegion |
1 review |
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) |
KCNA1 |
3 reviews1 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
KCNJ2 |
2 reviews1 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
KCNMA1 |
3 reviews1 green |
BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
KCNQ2 |
1 review1 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
KCNQ3 |
1 review1 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
PNKD |
3 reviews1 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
PRRT2 |
3 reviews1 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
SCN1A |
3 reviews1 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
SCN8A |
1 review1 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
SLC1A3 |
3 reviews1 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
SLC2A1 |
3 reviews1 green |
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
SLC6A5 |
1 review1 green |
BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
SPR |
1 review1 green |
BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
TBP_CAGSTR |
2 reviews |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Amber List (moderate evidence) |
KCNK18 |
3 reviews1 red |
Not set |
Sources
Phenotypes
Tags |
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Red List (low evidence) |
ATN1 |
2 reviews1 red |
Other |
Sources
Phenotypes
Tags |
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Red List (low evidence) |
HTT |
2 reviews1 red |
Other |
Sources
Phenotypes
Tags |
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Red List (low evidence) |
NKX2-1 |
1 review1 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Red List (low evidence) |
SCN9A |
2 reviews |
BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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No list |
HTT_CAGSTR |
3 reviews1 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
Promoted to V1. January 23 2017