Paediatric or syndromic cardiomyopathy
Gene: LDB3
Comment on mode of inheritance: There is sufficient evidence for the association of biallelic variants to paediatric dilated cardiomyopathy with green rating. However, only two unrelated cases with monoallelic variants had early-onset dilated Cardiomyopathy. Hence, the MOI should be changed to "BIALLELIC, autosomal or pseudoautosomal" and the rating should be updated to green in the next GMS review.Created: 18 Sep 2023, 8:20 p.m. | Last Modified: 18 Sep 2023, 8:24 p.m.
Panel Version: 3.33
As reviewed by Dmitrijs Rots, there are five unrelated cases reported with biallelic LDB3 variants and lethal paediatric dilated cardiomyopathy in PMID:36253531. It was also reported that these biallelic loss-of-function variants lead to an early-onset and more severe phenotype of cardiomyopathy and myopathy.
Monoallelic variants in LDB3 are associated with dilated cardiomyopathy with or without left ventricular noncompaction in both OMIM (MIM #601493) and Gene2Phenotype (with 'limited' rating in the DD panel). Two unrelated families reported in PMID:16427346, of which twin sisters from a family presented with isolated LVNC shortly after the brith, while male proband from second family was diagnosed at 13 years of age. The six unrelated patients with hypertrophic cardiomyopathy were diagnosed in the third to seventh decades of life (PMID:17097056).Created: 18 Sep 2023, 8:15 p.m. | Last Modified: 18 Sep 2023, 8:21 p.m.
Panel Version: 3.31
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Cardiomyopathy, dilated, 1C, with or without LVNC, OMIM:601493; dilated cardiomyopathy, MONDO:0005021
Publications
PMID: 36253531 describes 5 cases with lethal pediatric DCM due to biallelic LDB3 variantsCreated: 3 Sep 2023, 1:03 p.m. | Last Modified: 3 Sep 2023, 1:03 p.m.
Panel Version: 3.30
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
dilated cardiomyopathy
Publications
Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Amber on this panel.Created: 2 Dec 2019, 3:58 p.m. | Last Modified: 2 Dec 2019, 3:58 p.m.
Panel Version: 0.16
Cardiomyopathy, dilated, 1C, with or without LVNC OMIM#601493; Cardiomyopathy, hypertrophic, 24 OMIM#601493; Left ventricular noncompaction 3 OMIM#601493; Myopathy, myofibrillar, 4 OMIM#609452.Created: 25 Mar 2019, 4:30 p.m.
HGMD: Four variants assoc with DCM - only one DM. Haas 2015 lists 2 as VUS. Included in review of DCM genes: Dalin 2017 International Journal of Cardiology 228 (2017) 742748 and Hershberger 2013 Nat Rev Cardiol 10:531. Vatta J Am Coll Cardiol. 2003 Dec 3;42(11):2014-27: two paediatric onset cases but quite old literature.Created: 25 Mar 2019, 4:27 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: LDB3 were changed from Left ventricular noncompaction 3, with or without dilated cardiomyopathy; Cardiomyopathy, dilated 1C to Cardiomyopathy, dilated, 1C, with or without LVNC, OMIM:601493; dilated cardiomyopathy, MONDO:0005021
Publications for gene: LDB3 were set to
Mode of inheritance for gene: LDB3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Tag Q3_23_promote_green tag was added to gene: LDB3.
Source NHS GMS was added to LDB3. Source Expert Review Amber was added to LDB3. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
gene: LDB3 was added gene: LDB3 was added to Cardiomyopathies - including childhood onset. Sources: Expert Review Green,South West GLH Mode of inheritance for gene: LDB3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: LDB3 were set to Left ventricular noncompaction 3, with or without dilated cardiomyopathy; Cardiomyopathy, dilated 1C