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| Cardiomyopathy_Paediatric v0.175 | PKP2 | Elena Savva Mode of inheritance for gene: PKP2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cardiomyopathy_Paediatric v0.134 | MUT | Zornitza Stark Tag treatable tag was added to gene: MUT. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cardiomyopathy_Paediatric v0.104 | JPH2 | Zornitza Stark Mode of inheritance for gene: JPH2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cardiomyopathy_Paediatric v0.102 | RNF220 |
Zornitza Stark gene: RNF220 was added gene: RNF220 was added to Cardiomyopathy_Paediatric. Sources: Literature founder tags were added to gene: RNF220. Mode of inheritance for gene: RNF220 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNF220 were set to 33964137; 10881263 Phenotypes for gene: RNF220 were set to Leukodystrophy; CNS hypomyelination; Ataxia; Intellectual disability; Sensorineural hearing impairment; Elevated hepatic transaminases; Hepatic fibrosis; Dilated cardiomyopathy; Spastic paraplegia; Dysarthria; Abnormality of the corpus callosum Review for gene: RNF220 was set to GREEN Added comment: Sferra et al (2021 - PMID: 33964137) provide extensive evidence that biallelic RNF220 mutations cause a disorder characterized by hypomyelinating leukodystrophy, ataxia (9/9 - onset 1-5y), borderline intellectual functioning (3/9) / intellectual disability (5/9 - in most cases mild), sensorineural deafness (9/9) with complete hearing loss in the first decade of life, hepatopathy (9/9) with associated periportal fibrosis, and dilated cardiomyopathy (9/9) which was fatal. Other neurologic manifestations apart from ataxia incl. hyperreflexia (8/8), spastic paraplegia (9/9), dysarthria (9/9), peripheral neuropathy (4/9), seizures in one case (1/9). Upon brain MRI there was thin corpus callosum (9/9) or cerebellar atrophy in some (2/9). The authors identified homozygosity for 2 recurrent missense RNF220 variants in affected members belonging to these 5 broad consanguineous pedigrees (7 families), namely NM_018150.4:c.1094G>A / p.Arg365Gly in 4 Roma families in the context of a shared haplotype (/founder effect) as well as c.1088G>A / p.Arg363Gly in a large pedigree from southern Italy initially reported by Leuzzi et al (2000 - PMID: 10881263). Extensive segregation analyses were carried out including several affected and unaffected members. RNF220 encodes ring finger protein 220, which functions as an E3 ubiquitin ligase. Previous studies have shown among others a role in modulation of Sonic hedgehog/GLI signaling and cerebellar development Evidence for the role of RNF220 included relevant expression, localization within the cell, interaction partners (lamin B1, 20S proteasome), similarities with other laminopathies in terms of phenotype, etc : *RNF220 has a relevant expression pattern in CNS (based on qRT-PCR analyses in human brain, cerebellum, cerebral cortex / mRNA levels in human fetal CNS with higher expression in cerebellum, spinal cord and cortex / previous GTEx data / protein levels in mouse CNS) *The protein displays nuclear localization based on iPSC cells differentiated to motor neurons (also supported by data from the Human Protein Atlas). Transfection of COS-1 cells demonstrated localization primarily to the nucleus (as also previously demonstrated in HEK293T cells) in vesicle like structures with ASF2/SF2 colocalization suggesting enrichment in nuclear speckles. There was also partial co-distribution with the 20S proteasome. R363Q and R365Q additionally coalesced in the cytoplasm forming protein aggregates/inclusions. *Immunofluorescence studies in patient fibroblasts also confirmed abnormal increase of the protein in the cytoplasm and increased fluorescence with the 20S proteasome. *Proteomic identification of RNF220-interacting proteins in transfected HEK293T cells demonstrated enrichment for all members of the lamin protein family (incl . lamin B1, AC, B2). *RNAi-mediated downregulation of RNF222 in Drosophila suggested altered subcellular localization and accumulation of the fly orthologue for human lamin B1. *Immunoprecipitation of lamin B1 from the nuclear matrix of cerebellar cells suggested significant interaction of endogenous lamin B1 with RNF220, while transfection studies in HEK293T cells for wt/mt suggested reduced binding to endogenous lamin B1 for RNF220 mt compared to wt (more prominent for R365Q). RNF220 mutants also reduced ubiquitination of nuclear lamin B1 compared to wt. *Patient fibroblasts immunostained with different nuclear envelope markers displayed abnormal nuclear shapes with multiple invaginations and lobulations, findings also observed in laminopathies. Sources: Literature |
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| Cardiomyopathy_Paediatric v0.92 | NDUFB11 | Kristin Rigbye reviewed gene: NDUFB11: Rating: GREEN; Mode of pathogenicity: None; Publications: 28050600, 27488349, 30423443, 27488349; Phenotypes: Linear skin defects with multiple congenital anomalies 3, XLD (MIM#300952), Mitochondrial complex I deficiency, nuclear type 30, XLR (MIM#301021); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cardiomyopathy_Paediatric v0.65 | HSD17B10 | Zornitza Stark reviewed gene: HSD17B10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: HSD10 mitochondrial disease, MIM# 300438; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cardiomyopathy_Paediatric v0.65 | HSD17B10 |
John Christodoulou gene: HSD17B10 was added gene: HSD17B10 was added to Cardiomyopathy_Paediatric. Sources: Literature Mode of inheritance for gene: HSD17B10 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: HSD17B10 were set to PMID: 22127393 (review paper): PubMed: 20077426 (source paper) Phenotypes for gene: HSD17B10 were set to intellectual disability; regression; seizures; cardiomyopathy (dilated or hypertrophic); choreoathetosis; optic atrophy; retinal degeneration Penetrance for gene: HSD17B10 were set to Incomplete Review for gene: HSD17B10 was set to GREEN Added comment: OMIM - 300438 Sources: Literature |
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| Cardiomyopathy_Paediatric v0.62 | MIB1 |
Ain Roesley changed review comment from: PMID: 30322850 4x probands - all missense except frameshift. All absent in gnomAD except for Ser520Arg (5 hets, 0 homs) Only W271G and the fs demonstrated reduced NOTCh signaling Mutant zebrafish were evaluated for degree of malformation Association with LVNC disputed by clingen - 2 variants reported in PMID: 23314057 however the missense has 45 hets and the nonsense has 13 hets. Clingen also pointed out that there's too many carriers of LoF variants in gnomAD for gene association to be real NO association with DCM by clingen; to: CHD: PMID: 30322850 4x probands - all missense except frameshift. All absent in gnomAD except for Ser520Arg (5 hets, 0 homs) Only W271G and the fs demonstrated reduced NOTCh signaling Mutant zebrafish were evaluated for degree of malformation Association with LVNC disputed by clingen - 2 variants reported in PMID: 23314057 however the missense has 45 hets and the nonsense has 13 hets. Clingen also pointed out that there's too many carriers of LoF variants in gnomAD for gene association to be real NO association with DCM by clingen |
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| Cardiomyopathy_Paediatric v0.60 | MIB1 |
Ain Roesley changed review comment from: PMID: 30322850 4x probands - all missense except frameshift. All absent in gnomAD except for Ser520Arg (5 hets, 0 homs) Only W271G and the fs demonstrated reduced NOTCh signaling Mutant zebrafish were evaluated for degree of malformation Associated with LVNC disputed by clingen NO association with DCM by clingen; to: PMID: 30322850 4x probands - all missense except frameshift. All absent in gnomAD except for Ser520Arg (5 hets, 0 homs) Only W271G and the fs demonstrated reduced NOTCh signaling Mutant zebrafish were evaluated for degree of malformation Association with LVNC disputed by clingen - 2 variants reported in PMID: 23314057 however the missense has 45 hets and the nonsense has 13 hets. Clingen also pointed out that there's too many carriers of LoF variants in gnomAD for gene association to be real NO association with DCM by clingen |
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| Cardiomyopathy_Paediatric v0.0 | GLA |
Zornitza Stark gene: GLA was added gene: GLA was added to Cardiomyopathy_Paediatric. Sources: London South GLH,MetBioNet,Expert Review Amber,NHS GMS,South West GLH Mode of inheritance for gene: GLA was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: GLA were set to 27604308 Phenotypes for gene: GLA were set to Fabry disease, cardiac variant, 301500; Fabry disease (Sphingolipidoses); Fabry disease, 301500; Fabry Disease; HCM; syndromic HCM; Limb pain, angiokeratom; Fabry disease; HCM is a late complication in adults, also found in female carriers |
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| Cardiomyopathy_Paediatric v0.0 | COX7B |
Zornitza Stark gene: COX7B was added gene: COX7B was added to Cardiomyopathy_Paediatric. Sources: NHS GMS,Expert Review Amber,MetBioNet Mode of inheritance for gene: COX7B was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: COX7B were set to Linear skin defects with multiple congenital anomalies 2, 300887 |
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| Cardiomyopathy_Paediatric v0.0 | TAZ |
Zornitza Stark gene: TAZ was added gene: TAZ was added to Cardiomyopathy_Paediatric. Sources: London South GLH,MetBioNet,Expert Review Green,NHS GMS,South West GLH Mode of inheritance for gene: TAZ was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: TAZ were set to 27604308 Phenotypes for gene: TAZ were set to Barth syndrome, 302060; Dilated Cardiomyopathy, X-Linked; Left Ventricular Noncompaction Cardiomyopathy; Neutropenia, muscle weakness, growth retardation; Non-compaction cardiomyopathy; HCM, mixed; Disorders of mitochondrial membrane lipids (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of mitochondrial lipid metabolism; Methylglutaconic aciduria type II, Barth syndrome (Organic acidurias); Barth syndrome |
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| Cardiomyopathy_Paediatric v0.0 | NONO |
Zornitza Stark gene: NONO was added gene: NONO was added to Cardiomyopathy_Paediatric. Sources: NHS GMS,Expert Review Green Mode of inheritance for gene: NONO was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) |
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| Cardiomyopathy_Paediatric v0.0 | NDUFB11 |
Zornitza Stark gene: NDUFB11 was added gene: NDUFB11 was added to Cardiomyopathy_Paediatric. Sources: NHS GMS,MetBioNet,Expert Review Green Mode of inheritance for gene: NDUFB11 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: NDUFB11 were set to Linear skin defects with multiple congenital anomalies 3, 300952; ?Mitochondrial complex I deficiency, nuclear type 30, 301021 |
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| Cardiomyopathy_Paediatric v0.0 | NDUFA1 |
Zornitza Stark gene: NDUFA1 was added gene: NDUFA1 was added to Cardiomyopathy_Paediatric. Sources: NHS GMS,MetBioNet,Expert Review Green Mode of inheritance for gene: NDUFA1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: NDUFA1 were set to Mitochondrial complex I deficiency, nuclear type 12, 301020 |
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| Cardiomyopathy_Paediatric v0.0 | MUT |
Zornitza Stark gene: MUT was added gene: MUT was added to Cardiomyopathy_Paediatric. Sources: NHS GMS,South West GLH,MetBioNet,Expert Review Green Mode of inheritance for gene: MUT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MUT were set to 27604308 Phenotypes for gene: MUT were set to Dehydration, hepatomegaly, lethargy, coma, acidosis, high anion gap; Methylmalonic aciduria; Methylmalonic aciduria, mut(0) type 251000; DCM; Methylmalonyl-CoA mutase deficiency (Organic acidurias); Hypertrophic-hypocontractile cardiomyopathy; metabolic encephalopathy with hyperammonaemia, hypotonia, recurrent episodes of ketoacidosis, liver impairment, psychomotor retardation, recurrent infections. |
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| Cardiomyopathy_Paediatric v0.0 | LAMP2 |
Zornitza Stark gene: LAMP2 was added gene: LAMP2 was added to Cardiomyopathy_Paediatric. Sources: NHS GMS,South West GLH,London South GLH,Expert Review Green Mode of inheritance for gene: LAMP2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: LAMP2 were set to 27604308 Phenotypes for gene: LAMP2 were set to Danon disease; syndromic HCM |
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| Cardiomyopathy_Paediatric v0.0 | IDS |
Zornitza Stark gene: IDS was added gene: IDS was added to Cardiomyopathy_Paediatric. Sources: NHS GMS,MetBioNet,Expert Review Green Mode of inheritance for gene: IDS was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: IDS were set to 27604308 Phenotypes for gene: IDS were set to MPS II, Hunter disease (Mucopolysaccharidoses); MUCOPOLYSACCHARIDOSIS TYPE 2; Mucopolysaccharidosis Type II; Mucopolysaccharidosis II, 309900 |
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| Cardiomyopathy_Paediatric v0.0 | FHL1 |
Zornitza Stark gene: FHL1 was added gene: FHL1 was added to Cardiomyopathy_Paediatric. Sources: NHS GMS,South West GLH,Expert Review Green Mode of inheritance for gene: FHL1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: FHL1 were set to http://www.ncbi.nlm.nih.gov/pubmed/22523091 |
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| Cardiomyopathy_Paediatric v0.0 | EMD |
Zornitza Stark gene: EMD was added gene: EMD was added to Cardiomyopathy_Paediatric. Sources: NHS GMS,South West GLH,Expert Review Green Mode of inheritance for gene: EMD was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: EMD were set to Emery-Dreifuss muscular dystrophy 1, X-linked, 310300 |
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| Cardiomyopathy_Paediatric v0.0 | DMD |
Zornitza Stark gene: DMD was added gene: DMD was added to Cardiomyopathy_Paediatric. Sources: NHS GMS,South West GLH,Expert Review Green Mode of inheritance for gene: DMD was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: DMD were set to Duchenne muscular dystrophy, 310200; Cardiomyopathy, dilated, 3B; Dilated Cardiomyopathy, X-Linked; Becker muscular dystrophy, 300376 |
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