Activity
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6 actions
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| Leukodystrophy - paediatric v0.298 | ELP1 | Ain Roesley Marked gene: ELP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Leukodystrophy - paediatric v0.298 | ELP1 | Ain Roesley Gene: elp1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Leukodystrophy - paediatric v0.298 | ELP1 | Ain Roesley Classified gene: ELP1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Leukodystrophy - paediatric v0.298 | ELP1 | Ain Roesley Gene: elp1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Leukodystrophy - paediatric v0.297 | ELP1 | Sarah Pantaleo edited their review of gene: ELP1: Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Leukodystrophy - paediatric v0.297 | ELP1 |
Sarah Pantaleo gene: ELP1 was added gene: ELP1 was added to Leukodystrophy - paediatric. Sources: Literature Mode of inheritance for gene: ELP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ELP1 were set to PMID: 36864284 Phenotypes for gene: ELP1 were set to neurodevelopmental disorder, MONDO:0700092, ELP1-related Added comment: “A novel ELP1 mutation impairs the function of the Elongator complex and causes a severe neurodevelopment disorder”. The Elongator complex is suggested to play a role in NDDs, given that patient-derived mutations in its ELP2, ELP3, ELP4 and ELP6 subunits have been associated with these disorders. Pathogenic variants in ELP1 have been previously found in familial dysautonomia and medulloblastoma, with no link to NDDs affecting primarily the central nervous system. Clinical investigation included patient history and physical, neurological and MRI. A novel homozygous likely pathogenic ELP1 variant was identified by WGS (absent from gnomAD). Functional studies included in silico analysis of the mutated ELP1 in the context of the holo-complex, production and purification of the ELP1 harbouring the identified mutation and in vitro analyses. Report a novel missense mutation in the ELP1 identified in two siblings with ID and GDD (both less than 10 years old). The mutation is shown to perturb the ability of ELP123 to bind tRNAs and compromises the function of the Elongator in vitro and in human cells. Both sibling are non-verbal and had severe ID/GDD. MRI revealed white matter lesions with enlarged perivascular spaces, suggestive of an inflammatory reaction associate with demyelination. WGS identified c.2444A>C; p.(Lys815Thr), homozygous in both siblings. Consanguineous family. Parents heterozygous and asymptomatic. Carry out significant functional studies. Conclude that screening for ELP1 mutations “may be beneficial”. Sources: Literature |
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