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| Adult onset neurodegenerative disorder v2.277 | SPTLC1 |
James Polke gene: SPTLC1 was added gene: SPTLC1 was added to Neurodegenerative disorders - adult onset. Sources: NHS GMS Mode of inheritance for gene: SPTLC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SPTLC1 were set to 34059824; 34459874; 35627278; 35900868 Phenotypes for gene: SPTLC1 were set to Juvenile ALS Penetrance for gene: SPTLC1 were set to Incomplete Mode of pathogenicity for gene: SPTLC1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: SPTLC1 was set to GREEN Added comment: SPTLC1 previously associated with HSN1A but variants in these two publications associated with juvenile ALS. 34059824 and 35900868 propose a distinct pathomechanism of juvenile ALS variants (increased sphinganine systhesis) compared to HSN1A variants (shift to deoxysphinganine synthesis). At least 5 different variants now reported, almost all de-novo, but one family in 34059824 with p.Leu39del inherited from father with mild sensorimotor axonal neuropathy. Juvenile onset but inclusion on this adult panel in-line with current inclusion of ALS2 and SETX which also cause early onset ALS. No evidence that LoF variants cause HSN1A or juvenile ALS - GOF mechanisms demonstrated. Sources: NHS GMS |
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| Adult onset neurodegenerative disorder v2.184 | ALS2 | Arina Puzriakova Phenotypes for gene: ALS2 were changed from Primary lateral sclerosis, juvenile, 606353; Spastic paralysis, infantile onset ascending, 607225; Amyotrophic lateral sclerosis 2, juvenile, 205100 to Amyotrophic lateral sclerosis 2, juvenile, OMIM:205100; Primary lateral sclerosis, juvenile, OMIM:606353 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v2.45 | ALS2 | Ivone Leong Phenotypes for gene: ALS2 were changed from Primary lateral sclerosis, juvenile, 606353; Spastic paralysis, infantile onset ascending, 607225; Amyotrophic lateral sclerosis 2, juvenile, 205100; Amyotrophic Lateral Sclerosis, Recessive to Primary lateral sclerosis, juvenile, 606353; Spastic paralysis, infantile onset ascending, 607225; Amyotrophic lateral sclerosis 2, juvenile, 205100 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.101 | ALS2 | Louise Daugherty commented on gene: ALS2: Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group. All the green and amber, except for the genes with triplet repeats, were reviewed. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.100 | ALS2 | Louise Daugherty Source Wessex and West Midlands GLH was added to ALS2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.99 | ALS2 | Tracy Lester reviewed gene: ALS2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Primary lateral sclerosis, juvenile, 606353, Spastic paralysis, infantile onset ascending, 607225, Amyotrophic lateral sclerosis 2, juvenile, 205100, Amyotrophic Lateral Sclerosis, Recessive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.81 | ALS2 | Louise Daugherty Publications for gene ALS2 were changed from 12145748; 23881933; 25474699; 24503148 to 23881933; 24503148; 25474699; 12145748; 11586298 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.74 | ALS2 | Louise Daugherty commented on gene: ALS2: Review and rating submitted by Nick Beauchamp (Sheffield Diagnostic genetics Service), on behalf of Yorkshire and North East GLH for GMS Neurology specialist test group. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.72 | ALS2 | Nick Beauchamp reviewed gene: ALS2: Rating: GREEN; Mode of pathogenicity: ; Publications: 11586298; Phenotypes: Primary lateral sclerosis, juvenile, 606353, Spastic paralysis, infantile onset ascending, 607225, Amyotrophic lateral sclerosis 2, juvenile, 205100, Amyotrophic Lateral Sclerosis, Recessive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.67 | ALS2 | Louise Daugherty Source Yorkshire and North East GLH was added to ALS2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.11 | ALS2 | Louise Daugherty reviewed gene: ALS2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.10 | ALS2 | James Polke reviewed gene: ALS2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.9 | ALS2 | Louise Daugherty Source NHS GMS was added to ALS2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.8 | ALS2 | Louise Daugherty Source London North GLH was added to ALS2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v0.67 | ALS2 | Louise Daugherty Phenotypes for gene: ALS2 were changed from 607225; Primary lateral sclerosis, juvenile, 606353; Spastic paralysis, infantile onset ascending, 607225; Amyotrophic lateral sclerosis 2, juvenile, 205100; Amyotrophic Lateral Sclerosis, Recessive to Primary lateral sclerosis, juvenile, 606353; Spastic paralysis, infantile onset ascending, 607225; Amyotrophic lateral sclerosis 2, juvenile, 205100; Amyotrophic Lateral Sclerosis, Recessive | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v0.2 | ALS2 | Rebecca Foulger Added phenotypes 607225 for gene: ALS2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v0.2 | ALS2 |
Rebecca Foulger gene: ALS2 was added gene: ALS2 was added to Neurodegenerative disorders - adult onset. Sources: Expert Review Green Mode of inheritance for gene: ALS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ALS2 were set to 12145748; 23881933; 25474699; 24503148 Phenotypes for gene: ALS2 were set to Spastic paralysis, infantile onset ascending, 607225; Amyotrophic Lateral Sclerosis, Recessive; Amyotrophic lateral sclerosis 2, juvenile, 205100; Primary lateral sclerosis, juvenile, 606353 |
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