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  2. Amyotrophic lateral sclerosis/motor neuron disease

Amyotrophic lateral sclerosis/motor neuron disease (Version 1.74)

Level 3: Neurodegenerative disorders
Level 2: Neurology and neurodevelopmental disorders

Relevant disorders: Amyotrophic lateral sclerosis or motor neuron disease
Panel types: Rare Disease 100K
Previous code: 55d30b0322c1fc2ff2a5bf7b
Description
This panel is NO LONGER ACTIVELY MAINTAINED.

Please use with caution, as the gene list has not been recently updated. Reviews added to this panel are no longer a priority for curation and may not be followed up.

Please consider using an NHS Genomic Medicine Service (GMS) panel instead. The full list of GMS panels can be found here: https://nhsgms-panelapp.genomicsengland.co.uk/panels, with links back to PanelApp should you wish to leave a review on the panel.

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Amyotrophic lateral sclerosis or motor neuron disease inclusion criteria (29537)
- Progressive upper and/or lower motor neuron disease degeneration with clinical features of amyotrophy, spasticity, bulbar/pseudo-bulbar involvement  
- EMG/NCS consistent with MND 
- Positive family history of other affected family members with ALS or with FTD/ALS like phenotype or disease onset below 40 years.  

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.

Amyotrophic lateral sclerosis or motor neuron disease exclusion criteria (29537)
- Identified underlying cause for clinical syndrome e.g. multi-focal motor neuropathy, lymphoma

Prior genetic testing guidance (29537)
- 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.

Amyotrophic lateral sclerosis or motor neuron disease prior genetic testing genes (29537)
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: 
 - C9ORF72, SOD1

Closing statement (29537)
These requirements will be kept under continual review during the main programme and may be subject to change.
Panel Activity

15 reviewers

  • Ellen McDonagh (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Nayana Lahiri (South London GMC)

    Group: NHS Genomic Medicine Centre
    Workplace: NHS diagnostic lab

  • Arianna Tucci (Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square)

    Group: Other
    Workplace: Other

  • Caroline Wright (Genomics England Curator)

    Group: Other
    Workplace: Genomics England

  • Andrew Douglas (University of Southampton / Wessex Clinical Genetics Service)

    Group: NHS Genomic Medicine Centre
    Workplace: NHS clinical service

  • Sarah Leigh (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Alice Gardham (Genomics England)

    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

  • Ivone Leong (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Andrey Gagunashvili (UCL Great Ormond Street Institute of Child Health)

    Group: GeCIP domain
    Workplace: Other

  • Arina Puzriakova (Genomics England Curator)

    Group: Other
    Workplace: Other

  • David Collier (King's College London)

    Group: Other biotech or pharmaceutical
    Workplace: Research lab

  • Agnese Zarina (Rīga Stradiņš Univeristy)

    Group: Other
    Workplace: Other diagnostic lab

42 Entities

42 reviewed, 25 green

List Entity Reviews Mode of inheritance Details
42 Entitiess
Green List (high evidence)
ALS2
1 review
 BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Amyotrophic lateral sclerosis 2, juvenile, OMIM:205100
  • Primary lateral sclerosis, juvenile, OMIM:606353
Tags
Green List (high evidence)
ANG
1 review
 MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Amyotrophic Lateral Sclerosis, Dominant
  • Amyotrophic lateral sclerosis 9, 611895
  • familial amyotrophic lateral sclerosis (ALS9)
Tags
Green List (high evidence)
AR_CAG
STR
3 reviews
1 green 		X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Expert list
  • Expert Review Green
  • NHS GMS
Phenotypes
  • Spinal and bulbar muscular atrophy of Kennedy, OMIM:313200
Tags
  • STR
Green List (high evidence)
C9orf72_GGGGCC
STR
3 reviews
1 green 		MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert list
  • Expert Review Green
  • NHS GMS
Phenotypes
  • Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, OMIM:105550
Tags
  • STR
Green List (high evidence)
DCTN1
1 review
 MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Neuropathy, distal hereditary motor, type VIIB, 607641
  • {Amyotrophic lateral sclerosis, susceptibility to}, 105400
  • Perry syndrome, 168605
Tags
Green List (high evidence)
FIG4
2 reviews
 BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Amyotrophic lateral sclerosis 11 OMIM:612577
  • amyotrophic lateral sclerosis type 11 MONDO:0012945
  • Charcot-Marie-Tooth disease, type 4J, OMIM:611228
  • Charcot-Marie-Tooth disease type 4J MONDO:0012640
  • Yunis Varon syndrome OMIM:216340
  • Yunis-Varon syndrome MONDO:0008995
Tags
Green List (high evidence)
FUS
3 reviews
1 green 		MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Amyotrophic lateral sclerosis 6, autosomal recessive, with or without frontotemporal
  • Amyotrophic Lateral Sclerosis, Dominant
Tags
Green List (high evidence)
HNRNPA1
3 reviews
1 green 		MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • ?Inclusion body myopathy wtih early-onset Paget disease without frontotemporal
Tags
Green List (high evidence)
KIF5A
2 reviews
2 green 		MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • {Amyotrophic lateral sclerosis, susceptibility to, 25}, OMIM:617921
  • amyotrophic lateral sclerosis, susceptibility to, 25, MONDO:0060670
Tags
Green List (high evidence)
NEK1
2 reviews
1 green 		MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • ClinGen
  • Expert Review Green
  • Literature
  • Research
Phenotypes
  • Amyotrophic lateral sclerosis, susceptibility to, 24, OMIM:617892
  • amyotrophic lateral sclerosis, susceptibility to, 24, MONDO:0054750
Tags
Green List (high evidence)
NOP56_GGCCTG
STR
2 reviews
 MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review
  • Expert Review Green
  • NHS GMS
Phenotypes
  • Spinocerebellar ataxia 36, OMIM:614153
Tags
  • STR
Green List (high evidence)
OPTN
2 reviews
 BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Amyotrophic lateral sclerosis 12 with or without frontotemporal dementia, OMIM:613435
Tags
Green List (high evidence)
PFN1
3 reviews
1 green 		MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Amyotrophic lateral sclerosis 18, 614808
Tags
Green List (high evidence)
SETX
4 reviews
1 green 		BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Amyotrophic lateral sclerosis 4, juvenile, OMIM:602433
  • Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2, OMIM:606002
Tags
Green List (high evidence)
SIGMAR1
2 reviews
 BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Amyotrophic lateral sclerosis 16, juvenile, 614373
Tags
Green List (high evidence)
SLC52A2
2 reviews
1 green 		BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Expert Review Green
Phenotypes
  • Brown-Vialetto-Van Laere syndrome 2
Tags
  • treatable
Green List (high evidence)
SLC52A3
3 reviews
1 green 		BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Expert Review Green
Phenotypes
  • Brown-Vialetto-Van Laere syndrome 1
  • Fazio-Londe disease
Tags
Green List (high evidence)
SOD1
3 reviews
1 green 		BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Amyotrophic lateral sclerosis 1, OMIM:105400
Tags
Green List (high evidence)
SPAST
2 reviews
1 green 		MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Literature
  • Research
Phenotypes
  • Spastic paraplegia 4, autosomal dominant, OMIM:182601
  • hereditary spastic paraplegia 4, MONDO:0008438
Tags
Green List (high evidence)
TARDBP
3 reviews
2 green 		MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Amyotrophic Lateral Sclerosis, Dominant
  • Amyotrophic lateral sclerosis 10, with or without FTD, 612069
Tags
  • polygenic
Green List (high evidence)
TBK1
2 reviews
1 green 		MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Amyotrophic lateral sclerosis
  • fronto-temporal dementia
Tags
Green List (high evidence)
TUBA4A
2 reviews
1 green 		MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Amyotrophic lateral sclerosis 22 with or without frontotemporal dementia, OMIM:616208
  • amyotrophic lateral sclerosis type 22, MONDO:0014531
Tags
Green List (high evidence)
UBQLN2
2 reviews
 X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Expert
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Amyotrophic Lateral Sclerosis, Dominant
  • Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia, 300857
Tags
Green List (high evidence)
VAPB
1 review
 MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Amyotrophic Lateral Sclerosis, Dominant
  • Amyotrophic lateral sclerosis 8, 608627
Tags
Green List (high evidence)
VCP
1 review
 MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Amyotrophic lateral sclerosis 14, with or without frontotemporal dementia, 613954
  • Amyotrophic Lateral Sclerosis, Dominant
  • familial amyotrophic lateral sclerosis (ALS14)
Tags
Amber List (moderate evidence)
NEFH
3 reviews
 MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert list
  • Expert Review Amber
Phenotypes
  • susceptibility to amyotrophic lateral sclerosis (ALS)
Tags
Red List (low evidence)
AR
2 reviews
1 green 		Other
Sources
  • Expert Review
  • Expert Review Red
Phenotypes
  • Spinal and bulbar muscular atrophy of Kennedy, OMIM:313200
Tags
  • currently-ngs-unreportable
  • nucleotide-repeat-expansion
Red List (low evidence)
ATXN2
2 reviews
 Other
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • {Amyotrophic lateral sclerosis, susceptibility to, 13}, OMIM:183090
Tags
  • currently-ngs-unreportable
  • nucleotide-repeat-expansion
Red List (low evidence)
C9orf72
4 reviews
2 red 		Other
Sources
  • Eligibility statement prior genetic testing
  • Expert
  • Expert Review Red
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, OMIM:105550
Tags
  • currently-ngs-unreportable
  • nucleotide-repeat-expansion
Red List (low evidence)
CHCHD10
1 review
 Not set
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • ?Myopathy, isolated mitochondrial, autosomal dominant, 616209
Tags
Red List (low evidence)
CHMP2B
2 reviews
1 red 		MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Dementia, familial, nonspecific, 600795
  • Amyotrophic lateral sclerosis 17, 614696
Tags
Red List (low evidence)
ERBB4
3 reviews
2 red 		MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Amyotrophic lateral sclerosis 19, 615515
Tags
Red List (low evidence)
GRN
1 review
 MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert
  • Expert Review Red
Tags
Red List (low evidence)
HFE
1 review
 Unknown
Sources
  • Literature
Tags
Red List (low evidence)
SLC52A1
2 reviews
 MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert list
  • Expert Review Red
Phenotypes
  • Riboflavin deficiency (condition resembling childhood-onset motor neurone disease)
Tags
Red List (low evidence)
UNC13A
2 reviews
 Unknown
Sources
  • Literature
Tags
Red List (low evidence)
VEGFA
1 review
 Unknown
Sources
  • Literature
Tags
No list
ANXA11
2 reviews
 MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Literature
Phenotypes
  • Amyotrophic lateral sclerosis 23
Tags
No list
ATXN2_CAG
STR
3 reviews
1 green 		MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert list
  • Expert Review Removed
  • NHS GMS
Phenotypes
  • {Amyotrophic lateral sclerosis, susceptibility to, 13}, OMIM:183090
Tags
  • curated_removed
  • STR
No list
MATR3
1 review
 MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Literature
Phenotypes
  • Amyotrophic lateral sclerosis 21
Tags
No list
SPG11
2 reviews
1 green 		MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Literature
Phenotypes
  • Amyotrophic lateral sclerosis 5, juvenile
Tags
No list
SQSTM1
2 reviews
1 green 		MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Literature
Phenotypes
  • Frontotemporal dementia and/or amyotrophic lateral sclerosis 3
Tags

Major version comments

  • Promoted to version 1 on 19th December 2016 following external review and internal curation

Downloads

Download lists

  • Whole panel
  • Green list (high evidence)
  • Green and Amber Genes
  • Amber Genes
  • Red list (low evidence)

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