Paediatric or syndromic cardiomyopathy

Gene: LDB3

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 3 May 2024, 11:02 a.m. | Last Modified: 3 May 2024, 11:02 a.m.

Panel Version: 4.3

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

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

• 16427346
• 17097056
• 36253531

Green List (high evidence)

PMID: 36253531 describes 5 cases with lethal pediatric DCM due to biallelic LDB3 variants

Created: 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

• PMID: 36253531

I don't know

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

Red List (low evidence)

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