Is there a genetic test for X-Linked Tremors (Discovered in the English Springer Spaniel)?

X-Linked Tremors (Discovered in the English Springer Spaniel) is associated with the PLP1 gene. Where a validated DNA test for the causal variant is available, it can identify dogs carrying the variant before breeding. Per-breed variant frequency figures are published in the Sniff Atlas (242,664 dogs screened).

What is the human equivalent of X-Linked Tremors (Discovered in the English Springer Spaniel)?

OMIA links X-Linked Tremors (Discovered in the English Springer Spaniel) to its human counterpart in OMIM (OMIM 312080), the bridge to the deeper human-medicine literature for the same underlying biology.

Canine Mendelian disease record

X-Linked Tremors (Discovered in the English Springer Spaniel)

Q: How well studied is X-Linked Tremors (Discovered in the English Springer Spaniel) in dogs?

OMIA curates 15 peer-reviewed references for X-Linked Tremors (Discovered in the English Springer Spaniel). The full, linked citation list is on this page.

X-Linked Tremors (Discovered in the English Springer Spaniel). X-linked recessive. Observed in 0 of 266 breeds tested in the Sniff Atlas, with measured variant frequencies drawn from 242,664 dogs (Donner 2023). Whether a dog carrying this variant is at risk depends on the disease’s inheritance pattern; outcome also depends on penetrance, modifiers, and environment. The frequencies below describe variant prevalence, not confirmed disease incidence.

OMIA identifier: OMIA:000770-9615
Inheritance: X-linked recessive
Linked gene: PLP1
Human counterpart: In humans, this gene is PLP1. OMIM 300401 In people, variants in the PLP1 gene have conflicting classifications in ClinVar, and none is expert-reviewed. The evidence is unsettled, not that variants here are benign.
Source dataset: Sniff Atlas v1.0.1 / DOI

The human connection

A model of human Pelizaeus-Merzbacher spectrum disorder

Dogs with this condition carry a change in PLP1. In people, changes in the same gene cause Pelizaeus-Merzbacher spectrum disorder. 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.

In people, the disease is described as: An X-linked leukodystrophy characterized by developmental delay, nystagmus, hypotonia, spasticity, and variable intellectual deficit. It is classified into three sub-forms based on the age of onset and severity: connatal, transitional, and classic PMD.

In humans it is also called: HLD1, PMD, diffuse familial brain sclerosis, Pelizaeus Merzbacher disease, Pelizaeus-Merzbacher brain sclerosis.

MONDO:0010714 OMIM 312080 Mechanism (DisMech) →

Human mechanism pathograph for Pelizaeus-Merzbacher Disease is curated in DisMech (Monarch Initiative), joined by exact Mondo id. That page is about people. It is not a treatment plan for a dog.

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

X-linked hypomyelinating disorder, also called Pelizaeus-Merzbacher disease or hypomyelinating leukodystrophy 1

Clinical features

Affected Springer Spaniel dogs may be smaller than littermates, and often present with difficulty standing, ataxia, and generalised tremors that typically appear at 10-12 days of age (Griffiths et al., 1981). Death often occurs at 3-4 months of age (Griffiths et al., 1981; Nadon et al., 1990). IT thanks DVM student Judith Browne, who provided the basis of this contribution in May 2023.
Gutierrez-Quintana et al. (2026): "The most severely affected [English Cocker Spaniel] male pup displayed pronounced generalized tremors, progressive motor dysfunction, and markedly impaired growth."

Molecular genetics

By cloning and sequencing a very likely comparative candidate gene (based on the homologous disorder in humans, mice and rats), Nadon et al. (1990) reported the causative mutation as "a point mutation at position 219 of the coding sequence [of the PLP gene; now called PLP1] that results in a histidine to proline change in the protein". According to the current variant nomenclature as of 2013 this corresponds to a c.110A>C or p.H37P missense variant (omia.variant:82).
Gutierrez-Quintana et al. (2026) reported the disease in English Cocker Spaniel puppies and "identified a hemizygous c.92T>A missense variant in the PLP1 gene predicted to cause a leucine-to-glutamine substitution in the first transmembrane domain, p.(L31Q)" (omia.variant:1879) as likely causal variant.

Pathology

This disease is characterised by hypomyelination and reduced numbers of mature oligodendrocytes in the central nervous system (CNS) only, with abnormalities most pronounced in the cerebrum and optic nerve (Griffiths et al., 1981; Duncan et al., 1983). Histological features include shortened internodes, reduced thickness or absence of myelin sheaths of CNS axons, and expansion of the perinuclear sheaths and rough endoplasmic reticulum (RER) of oligodendrocytes (Griffiths et al., 1981; Duncan et al.,1983). Due to the X-linked mode of inheritance this disease affects males predominately. Due to X-inactivation in females, animals that are heterozygotes can present with tremors that disappear over time, and can present with myelin mosaicism in the CNS (Duncan et al., 1987). IT thanks DVM student Judith Browne, who provided the basis of this contribution in May 2023.

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 312080 Gene · OMIM 300401

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:000770-9615, doi:10.25910/2AMR-PV70 (CC-BY 4.0).

Signs & cross-references

How it presents

Catalogued in the Mondo disease ontology (the cross-species disease identity used by the Monarch Initiative) as Pelizeaus-Merzbacher spectrum disorder (MONDO:0010714).

Phenotype terms: Human Phenotype Ontology + Mammalian Phenotype Ontology; disease terms: Mondo (Monarch Initiative). Cross-references curated by OMIA (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 15.

A canine PLP1 missense variant differentiates oligodendrocyte maturation in connatal and classical Pelizaeus-Merzbacher disease. · Proc Natl Acad Sci U S A · 2026 · PMID 41701830
An overview of canine inherited neurological disorders with known causal variants. · Animals (Basel) · 2023 · PMID 38003185
A case of shaker dog disease in a miniature dachshund. · J Vet Med Sci · 2004 · PMID 15472486
Myelin mosaicism and brain plasticity in heterozygous females of a canine X-linked trait · Annals of Neurology · 1998 · PMID 9818933
Intracellular transport of the DM-20 bearing shaking pup (shp) mutation and its possible phenotypic consequences. · J Neurosci Res · 1997 · PMID 9418971
Molecular analysis of glial cell development in the canine shaking pup mutant · Developmental Neuroscience · 1996 · PMID 8894446

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.

Your breed

See what X-Linked Tremors (Discovered in the English Springer Spaniel) looks like in your dog's breed.

Variant frequency by breed

Observed only in small-sample breeds

Maximum variant 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.

Scope of this record

This record carries the breed-level carrier frequencies from the Donner 2023 cohort. Penetrance data (the fraction of at-risk dogs that develop the phenotype) is not yet quantified for this disease in the Sniff Atlas v1.0.1. The OMIA entry is the authoritative reference for the clinical phenotype, inheritance pattern, and gene assignment.

Predicted disease relevance at the per-dog level is UNPROVEN. The variant frequency is measured; phenotype outcome depends on 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:000770-9615.
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.

Gene page: PLP1, cited identity, disease associations, and the human-gene bridge.
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:000770-9615, authoritative clinical reference.
About OMIA, the catalogue this record comes from, and how Sniff uses it.

Last updated July 20, 2026

Sources: Sniff Atlas v1.0.1 · OMIA OMIA:000770-9615 · Donner et al. 2023 · ClinVar (Landrum 2018)