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| Motor Neurone Disease v2.1 | ATP13A2 |
Bryony Thompson gene: ATP13A2 was added gene: ATP13A2 was added to Motor Neurone Disease. Sources: Literature Mode of inheritance for gene: ATP13A2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATP13A2 were set to 40028680; 30992063 Phenotypes for gene: ATP13A2 were set to Kufor-Rakeb syndrome MONDO:0011706 Review for gene: ATP13A2 was set to GREEN Added comment: PMID 40028680 reports four individuals from two unrelated families with biallelic loss‑of‑function ATP13A2 variants (p.Arg487* homozygous; compound heterozygous p.Arg819* and p.Leu823Pro) presenting with an ALS‑like motor neuron disease characterised by progressive weakness, tongue fasciculations, spasticity, cognitive decline and juvenile‑onset parkinsonism. PMID 30992063 adds two unrelated families, one harbouring a homozygous nonsense p.Glu613Ter variant that segregates with disease and is absent from population databases, with functional zebrafish knock‑down and rescue confirming loss‑of‑function; the second family carries a homozygous missense p.Ile411Met variant present in gnomAD, which does not meet the qualifying variant criteria. Across the combined evidence, three independent families with qualifying biallelic loss‑of‑function variants fulfil the ≥3‑family threshold for Criterion A. The autosomal recessive inheritance and the recognisable ALS‑like phenotype are clinically actionable, supporting inclusion of ATP13A2 on the Motor Neurone Disease panel. Sources: Literature |
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| Motor Neurone Disease v2.0 | SPAST | Gene migrated from ENSG00000021574 to ENSG00000021574 (gene set migration) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Motor Neurone Disease v1.28 | ERLIN2 |
Bryony Thompson gene: ERLIN2 was added gene: ERLIN2 was added to Motor Neurone Disease. Sources: Literature Mode of inheritance for gene: ERLIN2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: ERLIN2 were set to 38607533; 38427163; 34734492; 32042907 Phenotypes for gene: ERLIN2 were set to hereditary spastic paraplegia 18 MONDO:0012639 Review for gene: ERLIN2 was set to GREEN gene: ERLIN2 was marked as current diagnostic Added comment: HSP phenoconversion to ALS has been reported in AD and AR families. Sources: Literature |
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| Motor Neurone Disease v0.47 | SPG7 |
Bryony Thompson gene: SPG7 was added gene: SPG7 was added to Motor Neuron Disease. Sources: Literature Mode of inheritance for gene: SPG7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SPG7 were set to 16765570; 19364936 Phenotypes for gene: SPG7 were set to Spastic paraplegia 7, autosomal recessive MIM#607259 Review for gene: SPG7 was set to GREEN Added comment: The HSP caused by this gene can be classified as a non-ALS MND, affecting the upper motor neurons. There are multiple reports of the condition mimicking MND. Sources: Literature |
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| Motor Neurone Disease v0.46 | SPAST | Bryony Thompson Marked gene: SPAST as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Motor Neurone Disease v0.46 | SPAST | Bryony Thompson Gene: spast has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Motor Neurone Disease v0.46 | SPAST | Bryony Thompson Classified gene: SPAST as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Motor Neurone Disease v0.46 | SPAST | Bryony Thompson Gene: spast has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Motor Neurone Disease v0.45 | SPAST |
Bryony Thompson gene: SPAST was added gene: SPAST was added to Motor Neuron Disease. Sources: Expert list Mode of inheritance for gene: SPAST was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SPAST were set to 16765570; 19364936 Review for gene: SPAST was set to GREEN Added comment: The HSP caused by this gene can be classified as a non-ALS MND, affecting the upper motor neurons. There are multiple reports of the condition mimicking MND. Sources: Expert list |
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| Motor Neurone Disease v0.43 | REEP1 |
Bryony Thompson gene: REEP1 was added gene: REEP1 was added to Motor Neuron Disease. Sources: Expert list Mode of inheritance for gene: REEP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: REEP1 were set to 23108492; 22703882 Phenotypes for gene: REEP1 were set to Spastic paraplegia 31, autosomal dominant MIM#610250 Review for gene: REEP1 was set to GREEN Added comment: The HSP caused by this gene can be classified as a non-ALS MND, affecting the upper and lower motor neurons. Sources: Expert list |
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| Motor Neurone Disease v0.39 | BSCL2 |
Bryony Thompson gene: BSCL2 was added gene: BSCL2 was added to Motor Neuron Disease. Sources: Expert list Mode of inheritance for gene: BSCL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: BSCL2 were set to 16765570 Phenotypes for gene: BSCL2 were set to Silver spastic paraplegia syndrome MIM#270685; Neuropathy, distal hereditary motor, type VA MIM#600794 Review for gene: BSCL2 was set to GREEN Added comment: The HSP and distal HMN caused by this gene can be classified as a non-ALS MND, affecting both upper and lower motor neurons. Sources: Expert list |
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| Motor Neurone Disease v0.37 | ATL1 |
Bryony Thompson gene: ATL1 was added gene: ATL1 was added to Motor Neuron Disease. Sources: Expert list Mode of inheritance for gene: ATL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATL1 were set to 16765570 Phenotypes for gene: ATL1 were set to Spastic paraplegia 3A, autosomal dominant MIM#182600 Review for gene: ATL1 was set to GREEN Added comment: The HSP caused by this gene can be classified as a non-ALS MND, affecting the upper motor neurons. Sources: Expert list |
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| Motor Neurone Disease v0.5 | SOD1 | Zornitza Stark Phenotypes for gene: SOD1 were changed from to Amyotrophic lateral sclerosis 1 (105400 AD, AR); Spastic tetraplegia and axial hypotonia, progressive (618598 AR) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Motor Neurone Disease v0.2 | SOD1 | Melanie Marty reviewed gene: SOD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8625408, 21545237, 16503123; Phenotypes: Amyotrophic lateral sclerosis 1 (105400 AD, AR), Spastic tetraplegia and axial hypotonia, progressive (618598 AR); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||