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| Mendeliome v1.4518 | RAB1A | Lucy Spencer Publications for gene: RAB1A were set to 37924809 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.4517 | RAB1A | Lucy Spencer Classified gene: RAB1A as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.4517 | RAB1A | Lucy Spencer Gene: rab1a has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.4516 | RAB1A |
Lucy Spencer changed review comment from: PMID: 37924809 2 families with PTCs inherited from affected fathers (Arg175* and Thr43fs), another proband with a PTC and unknown inheritance (Val22fs) and a 4th proband with a de novo missense (Leu28Pro). All variants were absent from gnomad except Val22fs which has a PTC within the first 102 nucleotides so is likely to escape NMD. Arg175* was in the last exon and also escapes NMD and removes two C-terminal prenylated cysteine residues that direct the subcellular localization and activity of Rab proteins. Studies in transfected cells showed a construct truncated protein failed to localise to the golgi. In KO cells both Arg175* and Leu28pro failed to rescue the phenotype. PMID: 38091987: two new probands with NDD and spasticity. One de novo for Ser200*, 2nd patient de novo for Arg175* same variant previously identified in a family from the previous paper. This new paper also says they have an aditional 3rd family with 2 affected siblings and an affected mother who also have Arg175*.; to: PMID: 37924809 2 families with PTCs inherited from affected fathers (Arg175* and Thr43fs), another proband with a PTC and unknown inheritance (Val22fs) and a 4th proband with a de novo missense (Leu28Pro). All variants were absent from gnomad except Val22fs which has a PTC within the first 102 nucleotides so is likely to escape NMD. Arg175* was in the last exon and also escapes NMD and removes two C-terminal prenylated cysteine residues that direct the subcellular localization and activity of Rab proteins. Studies in transfected cells showed a construct truncated protein failed to localise to the golgi. In KO cells both Arg175* and Leu28pro failed to rescue the phenotype. The individual with the missense variant had a more severe phenotype involving abnormal MRI findings and spondyloepimetaphyseal dysplasia, the functional studies suggested this variant has a dominant negative effect which would explain this. PMID: 38091987: two new probands with NDD and spasticity. One de novo for Ser200*, 2nd patient de novo for Arg175* same variant previously identified in a family from the previous paper. This new paper also says they have an aditional 3rd family with 2 affected siblings and an affected mother who also have Arg175*. |
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| Mendeliome v1.4516 | RAB1A | Lucy Spencer reviewed gene: RAB1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 37924809, 38091987; Phenotypes: neurodevelopmental disorder MONDO:0700092, RAB1A-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1416 | RAB1A | Zornitza Stark Marked gene: RAB1A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1416 | RAB1A | Zornitza Stark Gene: rab1a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1416 | RAB1A | Zornitza Stark Classified gene: RAB1A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1416 | RAB1A | Zornitza Stark Gene: rab1a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1415 | RAB1A |
Zornitza Stark gene: RAB1A was added gene: RAB1A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RAB1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RAB1A were set to 37924809 Phenotypes for gene: RAB1A were set to neurodevelopmental disorder MONDO:0700092, RAB1A-related Review for gene: RAB1A was set to AMBER Added comment: Four families and 5 individuals, 2/5 have speech delay and 4/5 have motor delay. Anxiety in 3/5 and autism in 2/5. Microcephaly in only one individual, spastic paraplegia observed in 2 individuals from one family. In 2 families variants were inherited from an affected parent. Sources: Literature |
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