OMIA:002796-9615 : Cardiomyopathy, dilated, LMNA-related in Canis lupus familiaris (dog) |
In other species: crab-eating macaque
Categories: Cardiovascular system phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 150330 (gene) , 115200 (trait)
Links to MONDO diseases:
Mendelian trait/disorder: yes
Mode of inheritance: Probably autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2023
Inheritance: Bannasch et al. (2023): "Pedigree analysis in the NSDTR [Nova Scotia Duck Tolling retriever] and functional evaluation of heterozygotes is consistent with a predominantly recessive mode of inheritance and possibly low penetrance in heterozygotes."
Mapping: (Bannasch et al., 2023): "Although DNA was initially only available from two [affected Nova Scotia Duck Tolling retrievers (NSDTR)], a genome-wide association study was performed using the two cases and 35 related, clinically unaffected NSDTR. Four candidate chromosomal regions homozygous in the cases were identified: chr7 (18693546–74786398), chr19 (33841298–34756758), chr24 (40956242–41731762), and a single SNP on chr3 (54049478)." This variant was identified by a combination of association mapping and whole genome sequence variant segregation using 131 dogs.
Molecular basis: Bannasch et al. (2023): "Whole genome sequencing identified a frameshift deletion in the LMNA gene (NC_049228.1:g.41688530del, NP_001274080:p.(Asp576ThrfsTer124)). ... The frameshift does not introduce a premature stop codon and is predicted to result in a mutant protein with 124 altered amino acids at its C-terminus (34 amino acids longer than the wildtype protein). ... Three retrospectively identified NSDTRs with sudden death before 2 years of age and severe myocardial fibrosis were also homozygous for the deletion. One 5 year old with sudden death and myocardial fibrosis was heterozygous for the deletion."
Genetic engineering:
Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing
Clinical features: Bannasch et al. (2023): "Two 10-month-old sibling Nova Scotia Duck Tolling Retrievers (NSDTR) died acutely with evidence of dilated cardiomyopathy with myocardial fibrosis." Abnormal Rhythm and dilated cardiomyopathy preceded sudden death in two cases. Three other cases presented with sudden death. When available necropsy of four cases showed severe myocardial fibrosis in dogs. All dogs homozygous for the mutant allele exhibited sudden death by 14 months of age. One related heterozygote had sudden death at 5 years of age.
Breed:
Nova Scotia Duck Tolling Retriever (Dog) (VBO_0200964).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
Associated gene:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| LMNA | lamin A/C | Canis lupus familiaris | 7 | NC_051811.1 (41586514..41569142) | LMNA | Homologene, Ensembl , NCBI gene |
Variants
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
| OMIA Variant ID | Breed(s) | Variant Phenotype | Gene | Allele | Type of Variant | Source of Genetic Variant | Reference Sequence | Chr. | g. or m. | c. or n. | p. | Verbal Description | EVA ID | Inferred EVA rsID | Year Published | PubMed ID(s) | Acknowledgements |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1638 | Nova Scotia Duck Tolling Retriever (Dog) | Cardiomyopathy, dilated, LMNA-related | LMNA | deletion, small (<=20) | Naturally occurring variant | UU_Cfam_GSD_1.0 | 7 | g.41688530del | c.1726del | p.(D576Tfs*124) | NM_001287151.1; NP_001274080 | 2023 | 37925523 |
Cite this entry
Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:002796-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70
References
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
| 2023 | Bannasch, D.L., Oertle, D.T., Vo, J., Batcher, K.L., Stern, J.A., Kaplan, J.L., Li, R.H.L., Madden, I.E., Christen, M., Leeb, T., Joshi, N. : |
| Naturally occurring canine laminopathy leading to a dilated and fibrosing cardiomyopathy in the Nova Scotia Duck Tolling Retriever. Sci Rep 13:19077, 2023. Pubmed reference: 37925523. DOI: 10.1038/s41598-023-46601-2. | |
| 2022 | Oertle, DT, Batcher, KL, Stern, JA, et al. : |
| Sudden death and cardiomyopathy associated with LMNA in the Nova Scotia Duck Tolling Retriever. Proceedings of the UC Davis Student Training in Advanced Research (STAR) Symposium , 2022. |
Edit History
- Created by Imke Tammen2 on 06 Nov 2023
- Changed by Imke Tammen2 on 06 Nov 2023
- Changed by Imke Tammen2 on 07 Nov 2023