Canine Mendelian disease record

Centronuclear Myopathy (Discovered in the Labrador Retriever; HACD1-related; CNM)

Q: What is the human equivalent of Centronuclear Myopathy (Discovered in the Labrador Retriever; HACD1-related; CNM)?

OMIA links Centronuclear Myopathy (Discovered in the Labrador Retriever; HACD1-related; CNM) to its human counterpart in OMIM (OMIM 619967), the bridge to the deeper human-medicine literature for the same underlying biology.

Q: How well studied is Centronuclear Myopathy (Discovered in the Labrador Retriever; HACD1-related; CNM) in dogs?

OMIA curates 17 peer-reviewed references for Centronuclear Myopathy (Discovered in the Labrador Retriever; HACD1-related; CNM). The full, linked citation list is on this page.

Centronuclear Myopathy (Discovered in the Labrador Retriever; HACD1-related; CNM). Autosomal recessive. Observed in 7 of 266 breeds tested in the Sniff Atlas, with measured carrier frequencies drawn from 242,622 dogs (Donner 2023). Per-dog phenotype outcome depends on penetrance, modifiers, and environment; the carrier frequencies below describe variant prevalence, not disease incidence.

OMIA identifier: OMIA:001374-9615
Inheritance: Autosomal recessive
Source dataset: Sniff Atlas v1.0.1 / DOI

The human connection

A model of human congenital myopathy 11

Dogs with this condition carry a change in HACD1. In people, changes in the same gene cause congenital myopathy 11. That makes affected dogs a naturally-occurring model of the human disease, and it is part of why studying dogs moves medicine forward for everyone. It does not mean your dog has the human disease. It means the two share an underlying biology.

MONDO:0859264 OMIM 619967

Mapped from OMIA via the human disease's OMIM entry to the Mondo Disease Ontology (Monarch Initiative, CC-BY 4.0). Sniff renders this as a model-of link; the canine disease remains the subject of this page.

About this disease

From OMIA's curated record

Documented in OMIA (Online Mendelian Inheritance in Animals). This describes the disease as recorded in the published literature, not a prediction for any individual dog. As of 2026-06-03.

Summary

Centronuclear Myopathy (CNM)

Clinical features

Centronuclear myopathy in Labradors presents with weakness, hypotonia, paresis and progressive skeletal muscle atrophy from at about 1 month of age (Walmsley et al., 2016). In rare cases, clinical signs may not become apparent until as late as 6 months of age. Affected dogs have abnormal deep tendon reflexes. Clinical signs become initially increasingly severe but may stabilise at approximately one year of age (Blot et al., 2002). There are a range of clinical presentations, ranging from mild disease with reduced exercise tolerance and gait abnormalities to more severe presentations involving obvious skeletal muscle atrophy and collapse. Dogs can have reduced muscle tone of the oesophagus leading to difficulties swallowing and a risk of sudden death, which can be reduced by gravity-assisted feeding (McKerrel & Braund, 1987). Clinical signs may be exacerbated by exposure to cold weather (McKerrel & Braund 1987). IT thanks DVM student Leo Rubinstein, who provided the basis of this contribution in May 2023.

Molecular genetics

Pelé et al. (2005) determined the molecular basis of this disorder by adopting a comparative positional cloning approach. Having mapped the canine disorder as described in the Mapping section above, they then studied the 208 human genes that are located in the orthologous region of chromosome HSA10p. Based on tissue expression and sequence motif, the most likely of these 208 genes was PTPLA (protein tyrosine phosphatase-like, member A). Sequencing of the canine PTPLA gene revealed the causative mutation as an insertion of a "tRNA-derived short interspersed repeat element (SINE)" in exon 2 ("PTPLA*g9459-9460ins236") which "has a striking effect on the maturation of PTPLA mRNA, whereby it can be spliced out, partially exonized or involved in multiple exon-skipping. As a result, the amount of wild-type transcripts falls to 1% in affected muscles." PTPLA is known as HACD1 in NCBI Gene.

Pathology

The skeletal muscle of affected dogs exhibits a number of characteristic changes including variation in fibre size, presence of angular fibres, altered oxidative staining, a predominance of type 1 myofibres, fibrosis and centralisation of nuclei (Walmsley et al., 2016). IT thanks DVM student Leo Rubinstein, who provided the basis of this contribution in May 2023.

Prevalence

Maurer et al. (2012) conducted a comprehensive world-wide survey by genotyping 7,426 Labradors from 18 countries for the PTPLA mutant reported by Pelé et al. (2005). All 80 affected dogs from 8 countries were homozygous for the same mutant allele, and none of the 1.172 heterozygous dogs from 13 countries was affected. The highest % of carriers were "found in the UK (19%), the USA (13%) and Canada (11,5%)". The UK estimate is similar to the UK estimate of 22%, reported by Owczarek-Lipska et al. (2011). Maurer et al. (2012) concluded that the mutant allele "resulted from a single and recent mutational event that may have rapidly disseminated through the extensive use of popular sires".

Inheritance

Tiret et al. (2003) showed that this disorder is autosomal recessive.

History

The first clinical description of this disorder was by Kramer et al. (1976).

Human analog

OMIA links this condition to its human counterpart in OMIM (Mendelian Inheritance in Man), the place to read across to the deeper human literature for the same biology.

Disease · OMIM 619967 Gene · OMIM 610467

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:001374-9615, doi:10.25910/2AMR-PV70 (CC-BY 4.0).

The evidence

Published references

The peer-reviewed papers behind this disease, curated by OMIA. Starred entries are OMIA-designated landmark papers. Showing 6 of 17.

The prevalence of nine genetic disorders in a dog population from Belgium, the Netherlands and Germany. · PLoS One · 2013 · PMID 24069350
Centronuclear myopathy in Labrador retrievers: a recent founder mutation in the PTPLA gene has rapidly disseminated worldwide. · PLoS One · 2012 · PMID 23071563
Frequency of the allelic variant of the PTPLA gene responsible for centronuclear myopathy in Labrador Retriever dogs as assessed in Italy. · J Vet Diagn Invest · 2011 · PMID 21217042
[Frequency of gene defects in selected European retriever populations]. · Schweiz Arch Tierheilkd · 2011 · PMID 21866517
SINE exonic insertion in the PTPLA gene leads to multiple splicing defects and segregates with the autosomal recessive centronuclear myopathy in dogs. · Hum Mol Genet · 2005 · PMID 15829503
The cnm locus, a canine homologue of human autosomal forms of centronuclear myopathy, maps to chromosome 2 · Human Genetics · 2003 · PMID 12884002

References curated by OMIA (Nicholas, Tammen & the Sydney Informatics Hub), doi:10.25910/2AMR-PV70 (CC-BY 4.0). Full list at the OMIA entry.

Predict a litter

Set each parent's status for Centronuclear Myopathy (Discovered in the Labrador Retriever; HACD1-related; CNM) and see the odds for their puppies. Single recessive variant, exact Mendelian math.

Parent A

Parent B

NNClear

NmCarrier

mmAffected

Clear25%

Carrier50%

Affected25%

These are the genetic odds for one known variant, not a promise: a real litter varies around them, and penetrance or other genes can change whether the condition ever appears. Use it to avoid pairing two carriers and to keep a line healthy, not to engineer a dog. Inheritance mode per OMIA.

Your breed

See what Centronuclear Myopathy (Discovered in the Labrador Retriever; HACD1-related; CNM) looks like in your dog's breed.

Carrier frequency by breed

Top 7 well-sampled breeds (n ≥ 50)

Maximum carrier frequency per breed across variants in the Donner 2023 cohort, with Wilson 95% confidence intervals. The list below is split into well-sampled breeds (n ≥ 50 tested) and small-sample breeds (n < 50, where the Wilson CI typically spans more than 20 percentage points and frequencies should not be compared directly to the well-sampled entries). Frequencies are population-level, not per-litter or per-line.

0%1%2%

Labrador Retriever1.0% · n 16,849

1.0%n 16,849

Dobermann Pinscher<0.1% · n 2,219

<0.1%n 2,219

Chihuahua<0.1% · n 4,271

<0.1%n 4,271

Boxer<0.1% · n 4,556

<0.1%n 4,556

Rottweiler<0.1% · n 4,716

<0.1%n 4,716

German Shepherd<0.1% · n 15,648

<0.1%n 15,648

American Staffordshire Terrier<0.1% · n 42,784

<0.1%n 42,784

n = 91,043 dogs · Donner et al. 2023 carrier-screening cohort · Sniff Atlas

Each bar is one well-sampled breed; the whisker is its Wilson 95% CI, and fainter bars have wider intervals. Frequencies are population-level, not per-litter. Carrier status for Centronuclear Myopathy (Discovered in the Labrador Retriever; HACD1-related; CNM) is measured; phenotype outcome depends on penetrance and modifiers.

▸ Full table with Wilson 95% confidence intervals

Breed	Carrier frequency	Wilson 95% CI	n tested
Labrador Retriever	1.0%	[0.9%, 1.2%]	16,849
Dobermann Pinscher	<0.1%	[0.0%, 0.2%]	2,219
Chihuahua	<0.1%	[0.0%, 0.1%]	4,271
Boxer	<0.1%	[0.0%, 0.1%]	4,556
Rottweiler	<0.1%	[0.0%, 0.1%]	4,716
German Shepherd	<0.1%	[0.0%, 0.0%]	15,648
American Staffordshire Terrier	<0.1%	[0.0%, 0.0%]	42,784

259 additional breeds in the Donner 2023 cohort were tested but showed no carriers.

Penetrance

From genotype to phenotype

Carrier status is not the same as disease status. Penetrance is the fraction of at-risk dogs that develop the phenotype. The Donner 2023 S4 table tracks this for 1 variant(s) underlying this disease in the cohort.

At-risk dogs evaluated: 2
Phenotype confirmed: 1
Penetrance range: not yet quantifiable

Predicted disease relevance at the per-dog level is UNPROVEN. The carrier frequency is measured; phenotype outcome is governed by penetrance, environment, and modifier loci. Consult a veterinarian for clinical interpretation.

How to cite this record

If you use this record in published work, cite the Sniff Atlas (the published dataset that carries the breed-level carrier frequencies) and the upstream sources:

Sniff Atlas v1.0.1 for the per-breed carrier frequencies:
Gehring, M. (2026). Sniff Atlas v1.0.1. Zenodo. https://doi.org/10.5281/zenodo.20566358. CC-BY 4.0.
OMIA for the disease definition, inheritance, and gene assignment:
Nicholas, F. W., & Tammen, I. (2024). OMIA. Sydney Informatics Hub, The University of Sydney. https://doi.org/10.25910/2AMR-PV70. Entry: OMIA:001374-9615.
Donner et al. 2023 for the breed × variant carrier-frequency cohort:
Donner, J., Freyer, J., Davison, S., Anderson, H., Blades, M., Honkanen, L., et al. (2023). Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs. PLOS Genetics, 19(2), e1010651. https://doi.org/10.1371/journal.pgen.1010651.

Full citation formats (BibTeX, RIS, CITATION.cff) at sniff.world/cite.

Sniff Atlas v1.0.1, the source dataset for these frequencies.
Browse breeds, per-breed Mendelian profiles, including this disease in context.
OMIA entry OMIA:001374-9615, authoritative clinical reference.
About OMIA, the catalogue this record comes from, and how Sniff uses it.

Last updated June 20, 2026

Sources: Sniff Atlas v1.0.1 · OMIA OMIA:001374-9615 · Donner et al. 2023