Limb-Girdle Muscular Dystrophy and Distal Myopathy

Gene: LDB3

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

• 36253531
• 32922198

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

• 26419279
• 16427346
• 14660611
• 14662268
• 27546599
• 25911362

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

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

• PMID: 27546599
• 25911362