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| Paediatric or syndromic cardiomyopathy v7.87 | DST |
Eleanor Williams gene: DST was added gene: DST was added to Paediatric or syndromic 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. 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. Created: 30 Sep 2025, 5:18 p.m. | Last Modified: 30 Sep 2025, 5:18 p.m. Sources: Literature |
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| Paediatric or syndromic cardiomyopathy v7.85 | PKD2 |
Achchuthan Shanmugasundram changed review comment from: Autosomal dominant variants in PKD2 gene are associated with Polycystic kidney disease 2 (MIM #613095, OMIM phenotype accessed on 07 September 2025). Reports on human patients: PMID:23376035 (2014) examined ADPKD database at Mayo clinic with 2,620 ADPKD patients seen between 1984 and 2010, where 374 patients were genotyped and 67 of them were identified with PKD2 variants. Of these 67, six patients from four different families had a diagnosis of idiopathic dilated cardiomyopathy (IDCM). The identified variants were p.Arg361Ter, p.Arg807Ter, c.423_430del8 and c.1095-5A>G. PMID:29270497 (2017) reported 3,885 ADPKD patients seen in the period between 1984 and 2015 in the same database as PMID:23376035, of which seven patients from four families had the same PKD2 variants. PMID:39472908 (2024) reported paediatric and adult probands with diverse cardiomyopathies from the UK 100,000 genomes project cohort, of which one adult male patient with hypertrophic cardiomyopathy was identified with a heterozygous stop-gain variant in PKD2 gene via analysis of data from singleton genome sequencing. Functional studies: PMID:23376035 (2014) studied Pkd2 mutant zebrafish, which showed low cardiac output and atrioventricular block. Isolated pkd2 mutant hearts displayed impaired intracellular calcium cycling and calcium alternans. These results indicate heart failure in the pkd2 mutants. PMID:27081851 (2016) reported that 9-month-old Pkd2+/- mice showed several anatomical features consistent with a dilated cardiac phenotype. However, Pkd2+/- 5-month-old mice did not present with a cardiac phenotype that paralleled either dilated cardiomyopathy or left ventricular hypertrophy, suggesting that PKD2 caused late-onset progressive cardiomyopathy. Sources: Literature; to: Autosomal dominant variants in PKD2 gene are associated with Polycystic kidney disease 2 (MIM #613095, OMIM phenotype accessed on 07 September 2025). Reports on human patients: PMID:23376035 (2014) examined ADPKD database at Mayo clinic with 2,620 ADPKD patients seen between 1984 and 2010, where 374 patients were genotyped and 67 of them were identified with PKD2 variants. Of these 67, six patients from four different families had a diagnosis of idiopathic dilated cardiomyopathy (IDCM). The identified variants were p.Arg361Ter, p.Arg807Ter, c.423_430del8 and c.1095-5A>G. PMID:29270497 (2017) reported 3,885 ADPKD patients seen in the period between 1984 and 2015 in the same database as PMID:23376035, of which seven patients from four families had the same PKD2 variants. PMID:39472908 (2024) reported paediatric and adult probands with diverse cardiomyopathies from the UK 100,000 genomes project cohort, of which one adult male patient with hypertrophic cardiomyopathy was identified with a heterozygous stop-gain variant in PKD2 gene (p.Arg213Ter) via analysis of data from singleton genome sequencing. Functional studies: PMID:23376035 (2014) studied Pkd2 mutant zebrafish, which showed low cardiac output and atrioventricular block. Isolated pkd2 mutant hearts displayed impaired intracellular calcium cycling and calcium alternans. These results indicate heart failure in the pkd2 mutants. PMID:27081851 (2016) reported that 9-month-old Pkd2+/- mice showed several anatomical features consistent with a dilated cardiac phenotype. However, Pkd2+/- 5-month-old mice did not present with a cardiac phenotype that paralleled either dilated cardiomyopathy or left ventricular hypertrophy, suggesting that PKD2 caused late-onset progressive cardiomyopathy. Sources: Literature |
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| Paediatric or syndromic cardiomyopathy v7.85 | PKD2 |
Achchuthan Shanmugasundram gene: PKD2 was added gene: PKD2 was added to Paediatric or syndromic cardiomyopathy. Sources: Literature Mode of inheritance for gene: PKD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PKD2 were set to 23376035; 27081851; 29270497; 39472908 Phenotypes for gene: PKD2 were set to Polycystic kidney disease 2, OMIM:613095; polycystic kidney disease 2, MONDO:0013131; dilated cardiomyopathy, MONDO:0005021 Review for gene: PKD2 was set to GREEN Added comment: Autosomal dominant variants in PKD2 gene are associated with Polycystic kidney disease 2 (MIM #613095, OMIM phenotype accessed on 07 September 2025). Reports on human patients: PMID:23376035 (2014) examined ADPKD database at Mayo clinic with 2,620 ADPKD patients seen between 1984 and 2010, where 374 patients were genotyped and 67 of them were identified with PKD2 variants. Of these 67, six patients from four different families had a diagnosis of idiopathic dilated cardiomyopathy (IDCM). The identified variants were p.Arg361Ter, p.Arg807Ter, c.423_430del8 and c.1095-5A>G. PMID:29270497 (2017) reported 3,885 ADPKD patients seen in the period between 1984 and 2015 in the same database as PMID:23376035, of which seven patients from four families had the same PKD2 variants. PMID:39472908 (2024) reported paediatric and adult probands with diverse cardiomyopathies from the UK 100,000 genomes project cohort, of which one adult male patient with hypertrophic cardiomyopathy was identified with a heterozygous stop-gain variant in PKD2 gene via analysis of data from singleton genome sequencing. Functional studies: PMID:23376035 (2014) studied Pkd2 mutant zebrafish, which showed low cardiac output and atrioventricular block. Isolated pkd2 mutant hearts displayed impaired intracellular calcium cycling and calcium alternans. These results indicate heart failure in the pkd2 mutants. PMID:27081851 (2016) reported that 9-month-old Pkd2+/- mice showed several anatomical features consistent with a dilated cardiac phenotype. However, Pkd2+/- 5-month-old mice did not present with a cardiac phenotype that paralleled either dilated cardiomyopathy or left ventricular hypertrophy, suggesting that PKD2 caused late-onset progressive cardiomyopathy. Sources: Literature |
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| Paediatric or syndromic cardiomyopathy v7.74 | GLA | Achchuthan Shanmugasundram reviewed gene: GLA: Rating: GREEN; Mode of pathogenicity: None; Publications: 39472908, 39620496, 39995634; Phenotypes: Fabry disease, OMIM:301500, Fabry disease, cardiac variant, OMIM:301500, Fabry disease, MONDO:0010526; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v7.18 | AIFM1 |
Achchuthan Shanmugasundram gene: AIFM1 was added gene: AIFM1 was added to Paediatric or syndromic cardiomyopathy. Sources: Literature Mode of inheritance for gene: AIFM1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: AIFM1 were set to 22019070; 28967629; 34117073; 39472908 Phenotypes for gene: AIFM1 were set to Combined oxidative phosphorylation deficiency 6, OMIM:300816 Review for gene: AIFM1 was set to GREEN Added comment: PMID:22019070 (2011) reported three siblings of Palestinian descent with early prenatal verntriculomegaly, of which two brothers were investigated further. The two brothers presented with infantile encephalomyopathy. One of them died at the age of 4 years due to cardiac failure secondary to aspiration pneumonia, and the other died at 3 months of age because of hypertrophic cardiomyopathy and aspiration pneumonia. Using linkage analysis in the family, followed by whole exome sequencing, a pathogenic variant in the AIFM1 gene was identified in patient B (c.923G > A/ p.Gly308Glu), which segregated with the disease state and was absent in 86 anonymous controls. PMID:28967629 (2018) reported two unrelated male patients with AIFM1 variants and they displayed distinct phenotypes including progressive ataxia which partially improved with riboflavin treatment. Cardiomyopathy was only reported in patient 2, who also displayed severe limb and palatal myoclonus, followed by ataxia, cerebellar atrophy, ophthalmoplegia, sensorineural hearing loss, and hyporeflexia. The c.422C > T (p.Thr141Ile) hemizygous variant was identified in this patient via WES and validated by Sanger sequencing and was confirmed de novo. PMID:34117073 (2021) reported three affected males (proband, brother and maternal uncle) exhibiting severe multisystem pathology, metabolic acidosis, and early demise. Biventricular hypertrophy was observed via foetal heart echocardiogram in the proband, and by limited autopsy in the maternal uncle. A missense hemizygous AIFM1 variant (c.506C > T/ p.Pro169Leu) was identified in the proband and sibling and this variant is absent in reference population databases, as discussed in this publication. PMID:39472908 (2024) reported paediatric and adult probands with diverse cardiomyopathies from the 100,000 genomes project, of which one male patient was identified with hemizygous variant in AIFM1 gene (c.603_605del/ p.Arg201del?). This gene is associated with Combined oxidative phosphorylation deficiency 6 (MIM #300816) in OMIM, which includes hypertrophic cardiomyopathy as one of the variable clinical presentations. Sources: Literature |
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| Paediatric or syndromic cardiomyopathy v7.17 | FBXL4 |
Achchuthan Shanmugasundram changed review comment from: PMID:23993193 (2013) reported three consanguineous families of Arab descent with homozygous FBXL4 loss-of-function mutations causing a lethal neonatal encephalopathy. The proband from family 2 presented in the first month of life with severe hypotonia, encephalopathy, cardiomyopathy, and lactic acidosis, leading to death at age 4 months. Three older siblings presented with a similar fatal, early-onset phenotype, and the proband’s mother has also suffered three miscarriages. Exome sequencing identified nonsense variant in FBXL4 (c.1303C>T/ p.(Arg435Ter)), predicting an earlier truncation of the protein than that observed in family 1. PMID:23993194 (2013) reported nine patients from seven unrelated families with FBXL4 variants causing early-onset mitochondrial encephalomyopathy. Two of these patients were reported with cardiac phenotypes: Prenatal ultrasound revealing growth retardation and dilated lateral ventricles in patient S7 (of Bahrain Arab descent) and echocardiography revealing left ventricular heart hypertrophy in patient S8 (of European descent). Patient S7 harboured homozygous missense variant (c.1652T>A/ p.(Ile551Asn)), while patient S8 harboured compound heterozygous variants – a nonsense and a missense variant in FBXL4 gene (c.614T>C; c.106A>T/ p.(Ile205Thr); p.(Arg36Ter]. PMID:25868664 (2015) reported 21 individuals from 19 different families of various ethnic backgrounds with biallelic FBXL4 variants and early-onset encephalopathic mitochondrial DNA depletion syndrome, of which three cases were previously reported in PMID:23993194 and one case was reported in PMID:23993193. Cardiac disease was observed at first presentation in seven individuals and evolved in another patient during the course and these patients included one from PMID:23993194. Cardiomyopathy (non-progressive or hypertrophic) was reported in four of these patients, while one other patient was reported with Borderline left-ventricular hypertrophy and hyperdynamic left ventricular function. PMID:26404457 (2016) reported a female neonate born to a French-Canadian mother with severe multisystem disease including lactic acidosis, cystic white matter lesions, cardiomyopathy, arrhythmias, and immunodeficiency. This patient was identified with homozygous frameshift variant in FBXL4 gene (c.1641_1642delTG; c.141del/ p.(Cys547Ter); p.(Asn48MetfsTer4)). PMID:28940506 (2017) reported 37 unreported individuals and 11 previously unreported pathogenic variants in addition to review of 36 FBXL4 variants from 50 affected individuals with a total of 87 patients and 47 variants. Hypertrophic cardiomyopathy, congenital heart disease and arrhythmia were reported in 20% (15/74), 19% (14/74) and 12% (9/78) patients respectively. PMID:39472908 (2024) reported paediatric and adult probands with diverse cardiomyopathies from the 100,000 genomes project, of which one patient was identified with compound heterozygous variants in FBXL4 variants (c.1641_1642del/ p.Cys547Ter There is also functional evidence available from mice model, where transfection of FBXL4 rescued the cardiac geometry and the mitochondrial integrity with altered mitochondrial dynamics in the adult mice model of the heart failure with preserved ejection fraction (PMID: 38359748). Sources: Literature; to: PMID:23993193 (2013) reported three consanguineous families of Arab descent with homozygous FBXL4 loss-of-function mutations causing a lethal neonatal encephalopathy. The proband from family 2 presented in the first month of life with severe hypotonia, encephalopathy, cardiomyopathy, and lactic acidosis, leading to death at age 4 months. Three older siblings presented with a similar fatal, early-onset phenotype, and the proband’s mother has also suffered three miscarriages. Exome sequencing identified nonsense variant in FBXL4 (c.1303C>T/ p.(Arg435Ter)), predicting an earlier truncation of the protein than that observed in family 1. PMID:23993194 (2013) reported nine patients from seven unrelated families with FBXL4 variants causing early-onset mitochondrial encephalomyopathy. Two of these patients were reported with cardiac phenotypes: Prenatal ultrasound revealing growth retardation and dilated lateral ventricles in patient S7 (of Bahrain Arab descent) and echocardiography revealing left ventricular heart hypertrophy in patient S8 (of European descent). Patient S7 harboured homozygous missense variant (c.1652T>A/ p.(Ile551Asn)), while patient S8 harboured compound heterozygous variants – a nonsense and a missense variant in FBXL4 gene (c.614T>C; c.106A>T/ p.(Ile205Thr); p.(Arg36Ter]. PMID:25868664 (2015) reported 21 individuals from 19 different families of various ethnic backgrounds with biallelic FBXL4 variants and early-onset encephalopathic mitochondrial DNA depletion syndrome, of which three cases were previously reported in PMID:23993194 and one case was reported in PMID:23993193. Cardiac disease was observed at first presentation in seven individuals and evolved in another patient during the course and these patients included one from PMID:23993194. Cardiomyopathy (non-progressive or hypertrophic) was reported in four of these patients, while one other patient was reported with Borderline left-ventricular hypertrophy and hyperdynamic left ventricular function. PMID:26404457 (2016) reported a female neonate born to a French-Canadian mother with severe multisystem disease including lactic acidosis, cystic white matter lesions, cardiomyopathy, arrhythmias, and immunodeficiency. This patient was identified with homozygous frameshift variant in FBXL4 gene (c.1641_1642delTG; c.141del/ p.(Cys547Ter); p.(Asn48MetfsTer4)). PMID:28940506 (2017) reported 37 unreported individuals and 11 previously unreported pathogenic variants in addition to review of 36 FBXL4 variants from 50 affected individuals with a total of 87 patients and 47 variants. Hypertrophic cardiomyopathy, congenital heart disease and arrhythmia were reported in 20% (15/74), 19% (14/74) and 12% (9/78) patients respectively. PMID:39472908 (2024) reported paediatric and adult probands with diverse cardiomyopathies from the 100,000 genomes project, of which one patient was identified with compound heterozygous variants in FBXL4 variants (c.1641_1642del/ p.Cys547Ter). There is also functional evidence available from mice model, where transfection of FBXL4 rescued the cardiac geometry and the mitochondrial integrity with altered mitochondrial dynamics in the adult mice model of the heart failure with preserved ejection fraction (PMID: 38359748). Sources: Literature |
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| Paediatric or syndromic cardiomyopathy v7.16 | FBXL4 |
Achchuthan Shanmugasundram gene: FBXL4 was added gene: FBXL4 was added to Paediatric or syndromic cardiomyopathy. Sources: Literature Mode of inheritance for gene: FBXL4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FBXL4 were set to 23993193; 23993194; 25868664; 26404457; 28940506; 38359748; 39472908 Phenotypes for gene: FBXL4 were set to Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), OMIM:615471 Review for gene: FBXL4 was set to GREEN Added comment: PMID:23993193 (2013) reported three consanguineous families of Arab descent with homozygous FBXL4 loss-of-function mutations causing a lethal neonatal encephalopathy. The proband from family 2 presented in the first month of life with severe hypotonia, encephalopathy, cardiomyopathy, and lactic acidosis, leading to death at age 4 months. Three older siblings presented with a similar fatal, early-onset phenotype, and the proband’s mother has also suffered three miscarriages. Exome sequencing identified nonsense variant in FBXL4 (c.1303C>T/ p.(Arg435Ter)), predicting an earlier truncation of the protein than that observed in family 1. PMID:23993194 (2013) reported nine patients from seven unrelated families with FBXL4 variants causing early-onset mitochondrial encephalomyopathy. Two of these patients were reported with cardiac phenotypes: Prenatal ultrasound revealing growth retardation and dilated lateral ventricles in patient S7 (of Bahrain Arab descent) and echocardiography revealing left ventricular heart hypertrophy in patient S8 (of European descent). Patient S7 harboured homozygous missense variant (c.1652T>A/ p.(Ile551Asn)), while patient S8 harboured compound heterozygous variants – a nonsense and a missense variant in FBXL4 gene (c.614T>C; c.106A>T/ p.(Ile205Thr); p.(Arg36Ter]. PMID:25868664 (2015) reported 21 individuals from 19 different families of various ethnic backgrounds with biallelic FBXL4 variants and early-onset encephalopathic mitochondrial DNA depletion syndrome, of which three cases were previously reported in PMID:23993194 and one case was reported in PMID:23993193. Cardiac disease was observed at first presentation in seven individuals and evolved in another patient during the course and these patients included one from PMID:23993194. Cardiomyopathy (non-progressive or hypertrophic) was reported in four of these patients, while one other patient was reported with Borderline left-ventricular hypertrophy and hyperdynamic left ventricular function. PMID:26404457 (2016) reported a female neonate born to a French-Canadian mother with severe multisystem disease including lactic acidosis, cystic white matter lesions, cardiomyopathy, arrhythmias, and immunodeficiency. This patient was identified with homozygous frameshift variant in FBXL4 gene (c.1641_1642delTG; c.141del/ p.(Cys547Ter); p.(Asn48MetfsTer4)). PMID:28940506 (2017) reported 37 unreported individuals and 11 previously unreported pathogenic variants in addition to review of 36 FBXL4 variants from 50 affected individuals with a total of 87 patients and 47 variants. Hypertrophic cardiomyopathy, congenital heart disease and arrhythmia were reported in 20% (15/74), 19% (14/74) and 12% (9/78) patients respectively. PMID:39472908 (2024) reported paediatric and adult probands with diverse cardiomyopathies from the 100,000 genomes project, of which one patient was identified with compound heterozygous variants in FBXL4 variants (c.1641_1642del/ p.Cys547Ter There is also functional evidence available from mice model, where transfection of FBXL4 rescued the cardiac geometry and the mitochondrial integrity with altered mitochondrial dynamics in the adult mice model of the heart failure with preserved ejection fraction (PMID: 38359748). Sources: Literature |
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| Paediatric or syndromic cardiomyopathy v7.9 | ASNA1 |
Achchuthan Shanmugasundram changed review comment from: As reviewed by Dmitrijs Rots, PMID:31461301 reported the identification of compound heterozygous variants in two siblings with early infantile-onset, rapidly progressive dilated cardiomyopathy. There were two variants reported on the paternal allele (p.Cys289Trp and p.Gln305Ter) and one variant on the maternal allele (p.Val163Ala). Unaffected sibling was heterozygous for maternal allele. Functional studies showed that Val163Ala variant leads to protein misfolding as well as less effective tail-anchored protein insertion. Loss of asna1 in zebrafish resulted in reduced cardiac contractility and early lethality. In contrast to wild-type mRNA, injection of either mutant mRNA failed to rescue this phenotype. As there is only one case and functional evidence available in support of this association, this gene can only be rated amber now.; to: PMID:31461301 reported the identification of compound heterozygous variants in two siblings with early infantile-onset, rapidly progressive dilated cardiomyopathy. There were two variants reported on the paternal allele (p.Cys289Trp and p.Gln305Ter) and one variant on the maternal allele (p.Val163Ala). Unaffected sibling was heterozygous for maternal allele. Functional studies showed that Val163Ala variant leads to protein misfolding as well as less effective tail-anchored protein insertion. Loss of asna1 in zebrafish resulted in reduced cardiac contractility and early lethality. In contrast to wild-type mRNA, injection of either mutant mRNA failed to rescue this phenotype. As there is only one case and functional evidence available in support of this association, this gene can only be rated amber now. |
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| Paediatric or syndromic cardiomyopathy v7.2 | MT-TL1 |
Achchuthan Shanmugasundram gene: MT-TL1 was added gene: MT-TL1 was added to Paediatric or syndromic cardiomyopathy. Sources: South West GLH,Expert Review,Expert Review Amber locus-type-rna-transfer tags were added to gene: MT-TL1. Mode of inheritance for gene gene: MT-TL1 was set to MITOCHONDRIAL Publications for gene: MT-TL1 were set to 7473662; 8477849; 12874464; 14673589; 25639022; 30888501; 30133155 Phenotypes for gene: MT-TL1 were set to MELAS syndrome caused by mutation in MTTL1, MONDO:0800032; hypertrophic cardiomyopathy, MONDO:0005045 |
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| Paediatric or syndromic cardiomyopathy v5.12 | NEXN | Eleanor Williams reviewed gene: NEXN: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v5.11 | NEXN | Eleanor Williams Mode of inheritance for gene NEXN 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v4.7 | NEXN | Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As reviewed by Hannah Robinson, there is sufficient evidence available for updating the MOI from 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' to 'BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal' in the next GMS update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v4.6 | NEXN | Achchuthan Shanmugasundram reviewed gene: NEXN: Rating: GREEN; Mode of pathogenicity: None; Publications: 32058062, 32058062, 35166435; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v4.3 | NEXN | Hannah Robinson reviewed gene: NEXN: Rating: ; Mode of pathogenicity: None; Publications: 35166435, 33949776, 33027564, 32058062; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v3.19 | NAA10 |
Achchuthan Shanmugasundram gene: NAA10 was added gene: NAA10 was added to Paediatric or syndromic cardiomyopathy. Sources: Literature Mode of inheritance for gene: NAA10 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: NAA10 were set to 29748569 Phenotypes for gene: NAA10 were set to Ogden syndrome, OMIM:300855 Review for gene: NAA10 was set to AMBER Added comment: PMID:29748569 reported the identification of previously undescribed NAA10 variant (c.215T>C; p.Ile72Thr) in three boys from two unrelated families with a milder phenotypic spectrum in comparison to most of the previously described patients with NAA10 variants. These boys had developmental delay, intellectual disability, and hypertrophic cardiomyopathy. This gene has been associated with Ogden syndrome in both OMIM ands Gene2Phenotype and the OMIM record includes hypertrophic cardiomyopathy and other cardiac abnormalities as clinical manifestations of this disorder. Sources: Literature |
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| Paediatric or syndromic cardiomyopathy v3.1 | TBX20 |
Matthew Edwards gene: TBX20 was added gene: TBX20 was added to Paediatric or syndromic cardiomyopathy. Sources: Other Mode of inheritance for gene: TBX20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TBX20 were set to PMID: 33585493; PMID: 275101702, PMID: 28798025; PMID: 32600061, PMID: 22080862 Phenotypes for gene: TBX20 were set to Cardiomyopathy, dilated with or without LVNC; Atrial septal defect, congential heart disease Penetrance for gene: TBX20 were set to unknown Review for gene: TBX20 was set to GREEN Added comment: TBX20 encodes transcription factors involved in the regulation of several important aspects of cardiac development and homeostasis and heart function. Pathogenic variants in TBX20 are widely associated with the complex spectrum of congenital heart defects and it has also been reported in association with dilated cardiomyopathies and heart arrhythmia (PMID: 33585493) Although loss of function (LoF) has not been clearly established as a disease mechanism for TBX20 in dilated cardiomyopathy (DCM) and left ventricular non-compaction (LVNC), several LoF alterations have been reported in individuals with these conditions, segregating with disease in several families (PMID: 275101702, PMID: 28798025). In addition mouse model studies have shown that mutant mice with conditional Tbx20 ablation in adult cardiomyocytes have dilated hearts with a rapid loss of systolic function and slower conduction and severe arrhythmia (PMID: 32600061, PMID: 22080862). A functional study ofa truncating variant identified in a DCM case, revealed that the truncated TBX20 protein had no transcriptional activity in contrast to its wild-type counterpart, which further supports the previous mouse model findings and LoF as a disease mechanism for DCM/LVNC (PMID: 275101702). Sources: Other |
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| Paediatric or syndromic cardiomyopathy v1.0 | MUT | Louise Daugherty Tag new-gene-name tag was added to gene: MUT. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v1.0 | MUT | Louise Daugherty commented on gene: MUT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.44 | TAZ | Ivone Leong Mode of inheritance for gene: TAZ was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.35 | NONO | Ivone Leong Mode of inheritance for gene: NONO was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.26 | FHL1 | Ivone Leong Mode of inheritance for gene: FHL1 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.16 | MUT | Ivone Leong reviewed gene: MUT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.15 | MUT | Ivone Leong Source NHS GMS was added to MUT. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.6 | COX7B |
Ivone Leong gene: COX7B was added gene: COX7B was added to Cardiomyopathies - including childhood onset. Sources: Expert Review Green,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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| Paediatric or syndromic cardiomyopathy v0.6 | NDUFB11 |
Ivone Leong gene: NDUFB11 was added gene: NDUFB11 was added to Cardiomyopathies - including childhood onset. Sources: Expert Review Green,MetBioNet 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 ?Mitochondrial complex I deficiency, nuclear type 30, 301021; Linear skin defects with multiple congenital anomalies 3, 300952 |
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| Paediatric or syndromic cardiomyopathy v0.6 | NDUFA1 |
Ivone Leong gene: NDUFA1 was added gene: NDUFA1 was added to Cardiomyopathies - including childhood onset. Sources: Expert Review Green,MetBioNet 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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| Paediatric or syndromic cardiomyopathy v0.1 | EMD |
Ivone Leong gene: EMD was added gene: EMD was added to Cardiomyopathies - including childhood onset. Sources: Expert Review Red,South West GLH 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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| Paediatric or syndromic cardiomyopathy v0.1 | TAZ |
Ivone Leong gene: TAZ was added gene: TAZ was added to Cardiomyopathies - including childhood onset. Sources: Expert Review Green,MetBioNet,London South GLH,South West GLH Mode of inheritance for gene: TAZ was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: TAZ were set to 27604308 Phenotypes for gene: TAZ were set to Disorders of mitochondrial lipid metabolism; Dilated Cardiomyopathy, X-Linked; Neutropenia, muscle weakness, growth retardation; Non-compaction cardiomyopathy; Barth syndrome, 302060; Left Ventricular Noncompaction Cardiomyopathy; HCM, mixed; Disorders of mitochondrial membrane lipids (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Barth syndrome; Methylglutaconic aciduria type II, Barth syndrome (Organic acidurias) |
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| Paediatric or syndromic cardiomyopathy v0.1 | MUT |
Ivone Leong gene: MUT was added gene: MUT was added to Cardiomyopathies - including childhood onset. Sources: Expert Review Green,MetBioNet,South West GLH 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 DCM; Methylmalonic aciduria, mut(0) type 251000; Hypertrophic-hypocontractile cardiomyopathy; Dehydration, hepatomegaly, lethargy, coma, acidosis, high anion gap; Methylmalonic aciduria; Methylmalonyl-CoA mutase deficiency (Organic acidurias); metabolic encephalopathy with hyperammonaemia, hypotonia, recurrent episodes of ketoacidosis, liver impairment, psychomotor retardation, recurrent infections. |
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| Paediatric or syndromic cardiomyopathy v0.1 | LAMP2 |
Ivone Leong gene: LAMP2 was added gene: LAMP2 was added to Cardiomyopathies - including childhood onset. Sources: Expert Review Green,London South GLH,South West GLH 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 syndromic HCM; Danon disease |
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| Paediatric or syndromic cardiomyopathy v0.1 | IDS |
Ivone Leong gene: IDS was added gene: IDS was added to Cardiomyopathies - including childhood onset. Sources: Expert Review Green,MetBioNet 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 II, 309900; Mucopolysaccharidosis Type II |
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| Paediatric or syndromic cardiomyopathy v0.1 | GLA |
Ivone Leong gene: GLA was added gene: GLA was added to Cardiomyopathies - including childhood onset. Sources: Expert Review Green,MetBioNet,London South GLH,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, 301500; HCM is a late complication in adults, also found in female carriers; Limb pain, angiokeratom; syndromic HCM; Fabry disease, cardiac variant, 301500; Fabry disease (Sphingolipidoses); Fabry Disease; Fabry disease; HCM |
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| Paediatric or syndromic cardiomyopathy v0.1 | FHL1 |
Ivone Leong gene: FHL1 was added gene: FHL1 was added to Cardiomyopathies - including childhood onset. Sources: Expert Review Green,South West GLH Mode of inheritance for gene: FHL1 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: FHL1 were set to http://www.ncbi.nlm.nih.gov/pubmed/22523091 |
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| Paediatric or syndromic cardiomyopathy v0.1 | DMD |
Ivone Leong gene: DMD was added gene: DMD was added to Cardiomyopathies - including childhood onset. Sources: Expert Review Green,South West GLH 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; Dilated Cardiomyopathy, X-Linked; Cardiomyopathy, dilated, 3B; Becker muscular dystrophy, 300376 |
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