OMIA:002796-9615 : Cardiomyopathy, dilated, LMNA-related in Canis lupus familiaris (dog)

In other species: crab-eating macaque

Categories: Cardiovascular system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 150330 (gene) , 115200 (trait)

Links to relevant human diseases in MONDO:

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."

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. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

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

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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 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.

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  • Created by Imke Tammen2 on 06 Nov 2023
  • Changed by Imke Tammen2 on 06 Nov 2023
  • Changed by Imke Tammen2 on 07 Nov 2023