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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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