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| Paediatric or syndromic cardiomyopathy v1.38 | NRAP |
Ivone Leong gene: NRAP was added gene: NRAP was added to Cardiomyopathies - including childhood onset. Sources: Literature Q2_21_rating tags were added to gene: NRAP. Mode of inheritance for gene: NRAP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NRAP were set to 30384889; 33534821; 28611399; https://doi.org/10.1101/2020.10.12.20211474; 32870709 Phenotypes for gene: NRAP were set to Dilated cardiomyopathy, MONDO:0005021 Edit Review for gene: NRAP was set to GREEN Added comment: This gene is Green on the Dilated cardiomyopathy - adult and teen (Version 1.22) with the following reviews: "This gene is not associated with a phenotype in OMIM or Gene2Phenotype. There are >3 unrelated cases of patients with variants in this gene and having DCM. https://doi.org/10.1101/2020.10.12.20211474 also describes a CRISPR knockout zebrafish which had a cardiac phenotype. Therefore, there is enough evidence to support a gene-disease association and this gene is recommended to be promoted Green at the next panel review. Sources: Literature Ivone Leong (Genomics England Curator), 25 Feb 2021" "Twenty unrelated families reported with childhood onset DCM. May be more appropriate for the paediatric cardiomyopathy panel." As affected individuals have childhood onset DCM it was deemed appropriate to add this gene to this panel as well. Sources: Literature |
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| Paediatric or syndromic cardiomyopathy v1.7 | MRAS |
Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is also Green on the RASopathies panel (v 1.61). Review copied from RASopathies panel: "Associated with Noonan syndrome in OMIM and G2P (confirmed). PMID: 28289718 (2017) - In two unrelated patients with Noonan syndrome and cardiac hypertrophy, trio WES/targeted sequencing revealed de novo missense variants (c.68G>T, p.G23V and c.203C>T, p.T68I) in the MRAS gene. Functional studies of the p.Gly23Val variant showed the change yields a constitutively active form of MRAS. PMID: 31173466 (2019) - One patient with a severe a Noonan syndrome phenotype, associated with a de novo MRAS variant (c.212A>G, p.Q71R). Functional studies were not performed. PMID: 31108500 (2020) - Two unrelated patients with Noonan syndrome, including hypertrophic cardiomyopathy and dysmorphic features. Targeted sequencing revealed de novo activating MRAS variants (c.203C>T, p.T68I and c.67G>C, p.G23R). Functional studies demonstrated that the variants yields a constitutively active form of MRAS. Arina Puzriakova (Genomics England Curator), 4 Aug 2020" Therefore, this gene will be promoted to Green status at the next major review. |
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| Paediatric or syndromic cardiomyopathy v0.16 | GLA | Ivone Leong reviewed gene: GLA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.15 | GLA |
Ivone Leong Source NHS GMS was added to GLA. Source Expert Review Amber was added to GLA. Rating Changed from Green List (high evidence) to Amber List (moderate evidence) |
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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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