Limb-Girdle Muscular Dystrophy and Distal Myopathy

Gene: LDB3

Green List (high evidence)

LDB3 (LIM domain binding 3)
EnsemblGeneIds (GRCh38): ENSG00000122367
EnsemblGeneIds (GRCh37): ENSG00000122367
OMIM: 605906, Gene2Phenotype
LDB3 is in 7 panels

3 reviews

Bryony Thompson (Royal Melbourne Hospital)

Green List (high evidence)

Comment on mode of inheritance: AD missense variants in LDB3 that affect only short isoforms are associated with skeletal myopathies, while AR LoF variants cause paediatric cardiomyopathy
Created: 27 Jul 2024, 1:41 a.m. | Last Modified: 27 Jul 2024, 1:41 a.m.
Panel Version: 1.1893
5 families with biallelic loss of function variants (homozygous & chet) with lethal/paediatric cardiomyopathy. Parents/heterozygotes appear to be unaffected. Also, knockdown mouse model suggesting deficiency induces DCM by mediating apoptosis in cardiomyocytes. Downregulation of Cypher (protein encoded by LDB3) induces apoptosis in vitro
Created: 27 Jul 2024, 1:38 a.m. | Last Modified: 27 Jul 2024, 1:38 a.m.
Panel Version: 1.1892

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
dilated cardiomyopathy MONDO:0005021

Publications

Ain Roesley (Victorian Clinical Genetics Services)

Green List (high evidence)

Myopathy is adult onset and green.

the association with DCM is limited as curated by ClinGen expert panel on May 22, 2020 (https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_7756e3c0-5a16-49b8-ac0f-220e79a4fa99-2020-09-25T160000.000Z)
Created: 7 Feb 2022, 12:04 a.m. | Last Modified: 7 Feb 2022, 12:04 a.m.
Panel Version: 0.10923

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cardiomyopathy, dilated, 1C, with or without LVNC MIM#601493; Cardiomyopathy, hypertrophic, 24 MIM#601493; Left ventricular noncompaction 3 MIM#601493; Myopathy, myofibrillar, 4 MIM#609452

Publications

Variants in this GENE are reported as part of current diagnostic practice

Elena Savva (Victorian Clinical Genetics Services)

Green List (high evidence)

OMIM: Onset in late adulthood (44 to 73 years)

PMID: 27546599 - 1 family with late onset muscle weakness (>50 years old), asymmetric muscle atrophy, cardiomyopathy and neuropathy. Paper reviews previous reports and notes age of onset was 25-73 years old with majority of patients in their 40s. A single report noted a 7 year-old child with a recurring missense variant (p.Ala165Val)

PMID: 25911362 - 1 family with lower limb weakness and myofibrillar myopathy. Proband reported weakness at ~55 years old, was heterozygous for the recurring missense variant (p.Ala165Val).

Summary: gene is green for adult onset myopathy, but red for paediatric
Created: 21 Jun 2020, 11:01 p.m. | Last Modified: 21 Jun 2020, 11:01 p.m.
Panel Version: 0.77

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Myopathy, myofibrillar, 4 609452

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Expert Review Green
  • Literature
Phenotypes
  • myofibrillar myopathy 4 MONDO:0012277
OMIM
605906
Clinvar variants
Variants in LDB3
Penetrance
None
Publications
Mode of Pathogenicity
Other
Panels with this gene

History Filter Activity

17 Apr 2023, Gel status: 3

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: ldb3 has been classified as Green List (High Evidence).

17 Apr 2023, Gel status: 3

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: ldb3 has been classified as Green List (High Evidence).

14 Apr 2023, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set mode of pathogenicity

Bryony Thompson (Royal Melbourne Hospital)

gene: LDB3 was added gene: LDB3 was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature Mode of inheritance for gene: LDB3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: LDB3 were set to 24668811; 27546599; 25911362 Phenotypes for gene: LDB3 were set to myofibrillar myopathy 4 MONDO:0012277 Mode of pathogenicity for gene: LDB3 was set to Other