Activity
| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
19 actions
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Possible mitochondrial disorder - nuclear genes v5.10 | PTPMT1 |
Arina Puzriakova Added comment: Comment on list classification: Following discussion with the Genomics England Clinical Team (William Macken and Helen Brittain) it was decided that it may be possible to classify this gene as green given the reasonably extensive functional work (further outlined below); however, inclusion should first be reviewed by the GMS expert team. As the phenotype is nonspecific, only tagging for promotion on more phenotypically broad panels. --- Functional evidence (PMID: 39279645): All patient fibroblasts showed decreased PTPMT1 protein expression. Cardiolipin content was decreased in one case but normal in another unrelated individual. Mitochondria in fibroblasts from 2 cases (distantly related) displayed fragmentation and abnormal shape - rescued using expression of WT PTPMT1. A ptpmt1 knockout zebrafish model showed abnormalities in head and body size, developmental alterations, decreased total cardiolipin levels and OXPHOS deficiency. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Possible mitochondrial disorder - nuclear genes v1.9 | ISCU | Sarah Leigh Classified gene: ISCU as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Possible mitochondrial disorder - nuclear genes v1.9 | ISCU | Sarah Leigh Added comment: Comment on list classification: Sufficient published reported biallelic cases, with supportive functional studies. The most frequent reported variant c.343+382G>C g.108567650G>C is deep in intron five of the gene and strengthens a weak splicing acceptor site, with consequent retention of a 100-bp intronic sequence upstream of the known terminal exon, introduction of a stop codon and decreased levels of ISCU mRNA and protein (PMID 18304497). This may be missed by standard sequencing. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Possible mitochondrial disorder - nuclear genes v1.9 | ISCU | Sarah Leigh Gene: iscu has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Possible mitochondrial disorder - nuclear genes v1.8 | ISCU | Sarah Leigh Publications for gene: ISCU were set to 18296749; 29079705; 19567699; 20206689 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Possible mitochondrial disorder - nuclear genes v1.7 | ISCU | Sarah Leigh Mode of inheritance for gene: ISCU was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Possible mitochondrial disorder - nuclear genes v1.6 | ISCU | Sarah Leigh Tag non-coding-known-pathogenic tag was added to gene: ISCU. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Possible mitochondrial disorder - nuclear genes v1.6 | ISCU | Sarah Leigh Publications for gene: ISCU were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Possible mitochondrial disorder - nuclear genes v1.5 | ISCU | Sarah Leigh Added comment: Comment on mode of inheritance: A recently reported de novo dominant variant in ISCU associated with mitochondrial myopathy (PMID 29079705), justifies the mode of inheritance listed here (in consultation with the GMS Mitochondrial specialist test group). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Possible mitochondrial disorder - nuclear genes v1.5 | ISCU | Sarah Leigh Mode of inheritance for gene: ISCU was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Possible mitochondrial disorder - nuclear genes v0.129 | TOP3A | Ellen McDonagh Added comment: Comment on list classification: The evidence underlying this gene and mitochondrial DNA maintenance disorders was discussed on the NHSE GMS Mitochondrial Specialist Group Meeting call on 25th February 2019. It was agreed that this gene should be demoted from Green to Amber on this panel due to only a single case (compound heterozygous for variants in this gene) being reported Progressive external ophthalmoplegia with mitochondrial DNA deletions. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Possible mitochondrial disorder - nuclear genes v0.127 | TIMMDC1 | Ellen McDonagh Added comment: Comment on list classification: Single report of 3 unrelated cases with SAME INTRONIC VARIANT and expression data but no other functional work. Demoted from Green to Amber after discussion on the on the NHSE GMS Mitochondrial Specialist Group Meeting call on 25th February 2019. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Possible mitochondrial disorder - nuclear genes v0.112 | ISCU | Ellen McDonagh Tag founder-effect tag was added to gene: ISCU. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Possible mitochondrial disorder - nuclear genes v0.108 | ECSIT | Ellen McDonagh Added comment: Comment on list classification: The evidence underlying this gene-disease was discussed on the NHSE GMS Mitochondrial Specialist Group Meeting call on 25th February 2019. It was confirmed that this gene should be Red due to insufficient evidence; no cases have yet been reported in the literature and its role is not yet completely understood. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Possible mitochondrial disorder - nuclear genes v0.17 | SLC25A22 | Ellen McDonagh Added comment: Comment on list classification: This gene-disease was discussed on the NHSE GMS Mitochondrial Specialist Group Meeting call on 25th February 2019, and it was decided to promote this gene from Amber to Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Possible mitochondrial disorder - nuclear genes v0.10 | IDH3B | Ellen McDonagh Added comment: Comment on list classification: This gene-disease was discussed on the NHSE GMS Mitochondrial Specialist Group Meeting call on 25th February 2019, and the decision was made to make this gene Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Possible mitochondrial disorder - nuclear genes v0.9 | HARS2 | Ellen McDonagh Added comment: Comment on list classification: This gene was discussed on the NHSE GMS Mitochondrial Specialist Group Meeting call on 25th February 2019. It was confirmed that Perrault syndrome was relevant for this panel, and that there was enough evidence for the gene to be Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Possible mitochondrial disorder - nuclear genes v0.5 | ISCU | Ivone Leong reviewed gene: ISCU: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Myopathy with lactic acidosis, hereditary, 255125; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Possible mitochondrial disorder - nuclear genes v0.2 | ISCU |
Ivone Leong gene: ISCU was added gene: ISCU was added to Possible mitochondrial disorder - nuclear genes. Sources: Expert Review Green,NHS GMS Mode of inheritance for gene: ISCU was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ISCU were set to Myopathy with lactic acidosis, hereditary, 255125 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||