Activity
| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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15 actions
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| Dilated and arrhythmogenic cardiomyopathy v3.6 | DST | Eleanor Williams Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v3.6 | DST | Eleanor Williams edited their review of gene: DST: Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v3.6 | DST | Eleanor Williams Tag curated_removed tag was added to gene: DST. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v3.6 | DST | Eleanor Williams Classified gene: DST as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v3.6 | DST | Eleanor Williams Added comment: Comment on list classification: Removing from this panel. Since the presentation is syndromic it is better suited to the Paediatric or syndromic cardiomyopathy panel (panel ID 749) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v3.6 | DST | Eleanor Williams Gene: dst has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v3.5 | DST | Eleanor Williams Classified gene: DST as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v3.5 | DST | Eleanor Williams Gene: dst has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v3.4 | DST | Eleanor Williams changed review comment from: Comment on list classification: Promoting to amber with a recommendation for green rating following GMS approval.; to: Comment on list classification: Promoting to amber but checking with the clinical team whether this is the right panel for this gene. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v3.4 | DST | Eleanor Williams Tag Q3_25_promote_green was removed from gene: DST. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v3.4 | DST |
Eleanor Williams changed review comment from: Associated with Epidermolysis bullosa simplex 3, localized or generalized intermediate, with bp230 deficiency (615425) and Neuropathy, hereditary sensory and autonomic, type VI (614653) in OMIM caused by a loss of DST-e and DST-a respectively. PMID: 40497796 (2025) - biallelic variants in the DST impacting the DST-b isoform were identified in in 19 individuals from 14 unrelated families of different ethnicities by exome or genome sequencing or Sanger sequencing of affected siblings. Other likely pathogenic variants were excluded through sequencing analysis in line with ACMG classification guidelines. 8 variants were identified in these 19 patients with variants that only affect the DST-b isoform; 4 nonsense and 4 frameshift. All variants were absent or rare in gnomad. In 13 families the variant was homozygous and in 1 it was compound heterozygous. Prenatal abnormalities were documented in 7/15 cases (reduced fetal movements and joint contractures). Of the 16 individuals assessed post birth, all displayed contractures at birth, 10/14 (from 9 families) displayed cardiomyopathy (9 with dilated cardiomyopathy), 14/14 (from 12 families) motor delay and 15/15 (from 12 families) muscular hypotonia. RNA sequencing from control individuals showed that transcripts encoding DST-b isoform are expressed in skeletal muscle, heart tissue, and cultured fibroblasts. RNA sequencing analysis of patient fibroblasts from 3 affected individuals showed reduced DST RNA levels, but only in one case was this statistically signficant. However, proteomic studies with fibroblasts from 2 individuals showed a significant reduction of Dystonin, and a complete loss of the DST-b isoform. The author conclude this indicates that the DST-b transcripts escape NMD but encode a protein that is instable or rapidly degraded. In addition, biallelic variants affecting both DST-a and DST-b isoforms were identified in 4 individuals from two families by exome sequencing. All presented with severe arthrogryposis and died intrauterine or shortly after birth. PMID: 35942699 (2022) In a Dst-b-specific mutant mouse model with a nonsense mutation, the mice exhibit late-onset protein aggregate myopathy and cardiomyopathy without neuropathy. Sources: Literature; to: Associated with Epidermolysis bullosa simplex 3, localized or generalized intermediate, with bp230 deficiency (615425) and Neuropathy, hereditary sensory and autonomic, type VI (614653) in OMIM caused by a loss of DST-e and DST-a respectively. However, variants in the DTS-b isoform appear to result in a different phenotype. PMID: 40497796 (2025) - biallelic variants in the DST impacting the DST-b isoform were identified in in 19 individuals from 14 unrelated families of different ethnicities by exome or genome sequencing or Sanger sequencing of affected siblings. Other likely pathogenic variants were excluded through sequencing analysis in line with ACMG classification guidelines. 8 variants were identified in these 19 patients with variants that only affect the DST-b isoform; 4 nonsense and 4 frameshift. All variants were absent or rare in gnomad. In 13 families the variant was homozygous and in 1 it was compound heterozygous. Prenatal abnormalities were documented in 7/15 cases (reduced fetal movements and joint contractures). Of the 16 individuals assessed post birth, all displayed contractures at birth, 10/14 (from 9 families) displayed cardiomyopathy (9 with dilated cardiomyopathy), 14/14 (from 12 families) motor delay and 15/15 (from 12 families) muscular hypotonia. RNA sequencing from control individuals showed that transcripts encoding DST-b isoform are expressed in skeletal muscle, heart tissue, and cultured fibroblasts. RNA sequencing analysis of patient fibroblasts from 3 affected individuals showed reduced DST RNA levels, but only in one case was this statistically signficant. However, proteomic studies with fibroblasts from 2 individuals showed a significant reduction of Dystonin, and a complete loss of the DST-b isoform. The author conclude this indicates that the DST-b transcripts escape NMD but encode a protein that is instable or rapidly degraded. In addition, biallelic variants affecting both DST-a and DST-b isoforms were identified in 4 individuals from two families by exome sequencing. All presented with severe arthrogryposis and died intrauterine or shortly after birth. PMID: 35942699 (2022) In a Dst-b-specific mutant mouse model with a nonsense mutation, the mice exhibit late-onset protein aggregate myopathy and cardiomyopathy without neuropathy. Sources: Literature |
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| Dilated and arrhythmogenic cardiomyopathy v3.4 | DST | Eleanor Williams Classified gene: DST as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v3.4 | DST | Eleanor Williams Added comment: Comment on list classification: Promoting to amber with a recommendation for green rating following GMS approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v3.4 | DST | Eleanor Williams Gene: dst has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v3.3 | DST |
Eleanor Williams gene: DST was added gene: DST was added to Dilated and arrhythmogenic cardiomyopathy. Sources: Literature Q3_25_promote_green tags were added to gene: DST. Mode of inheritance for gene: DST was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DST were set to 40497796; 35942699 Phenotypes for gene: DST were set to arthrogryposis, MONDO:0859248; cardiomyopathy, MONDO:0004994; congenital myopathy, MONDO:0019952 Review for gene: DST was set to GREEN Added comment: Associated with Epidermolysis bullosa simplex 3, localized or generalized intermediate, with bp230 deficiency (615425) and Neuropathy, hereditary sensory and autonomic, type VI (614653) in OMIM caused by a loss of DST-e and DST-a respectively. PMID: 40497796 (2025) - biallelic variants in the DST impacting the DST-b isoform were identified in in 19 individuals from 14 unrelated families of different ethnicities by exome or genome sequencing or Sanger sequencing of affected siblings. Other likely pathogenic variants were excluded through sequencing analysis in line with ACMG classification guidelines. 8 variants were identified in these 19 patients with variants that only affect the DST-b isoform; 4 nonsense and 4 frameshift. All variants were absent or rare in gnomad. In 13 families the variant was homozygous and in 1 it was compound heterozygous. Prenatal abnormalities were documented in 7/15 cases (reduced fetal movements and joint contractures). Of the 16 individuals assessed post birth, all displayed contractures at birth, 10/14 (from 9 families) displayed cardiomyopathy (9 with dilated cardiomyopathy), 14/14 (from 12 families) motor delay and 15/15 (from 12 families) muscular hypotonia. RNA sequencing from control individuals showed that transcripts encoding DST-b isoform are expressed in skeletal muscle, heart tissue, and cultured fibroblasts. RNA sequencing analysis of patient fibroblasts from 3 affected individuals showed reduced DST RNA levels, but only in one case was this statistically signficant. However, proteomic studies with fibroblasts from 2 individuals showed a significant reduction of Dystonin, and a complete loss of the DST-b isoform. The author conclude this indicates that the DST-b transcripts escape NMD but encode a protein that is instable or rapidly degraded. In addition, biallelic variants affecting both DST-a and DST-b isoforms were identified in 4 individuals from two families by exome sequencing. All presented with severe arthrogryposis and died intrauterine or shortly after birth. PMID: 35942699 (2022) In a Dst-b-specific mutant mouse model with a nonsense mutation, the mice exhibit late-onset protein aggregate myopathy and cardiomyopathy without neuropathy. Sources: Literature |
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