OMIA 002389-9685 : Spinal muscular atrophy, LIX1-related in Felis catus

Possibly relevant human trait(s) and/or gene(s) (MIM number): 610466 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2006

Species-specific description: Feline spinal muscular atrophy is a neurogenic disease characterized by progressive gait abnormalities, weakness, and atrophy of limb muscles. It is present in Maine Coon cats. Signs appear between 13 and 17 weeks of age, and include gait abnormalities, tremors, weakness, muscle atrophy, elevations of creatine phosphokinase activity, and abnormal electrical activity of muscles on EMG. Pathologic changes are consistent with muscle denervation, which is due to lower motor neuron loss. The mode of inheritance is autosomal recessive. The causative mutation is a deletion removing portions of LIX1 and LNPEP. There is a test available to detect the mutation. Maine Coon cats used for breeding should be tested for the causative mutation. Affected cats should not be bred. Carriers should only be bred to tested cats demonstrated to be noncarriers.

Edited by John C. Fyfe, D.V.M., Ph.D.

Mapping: FCA (A1q)

Molecular basis: The causative mutation is a ~140 kb deletion removing exons 4-6 of LIX1 and all except exon 1 of LNPEP (Fyfe et al., 2006).

Clinical features: Affected cats begin to show signs between 13 and 17 weeks of age. Signs include gait abnormalities, and a muscle tremor primarily involving the hindquarters. Limb weakness is progressive for several months. By five months of age, muscle atrophy is evident in all limbs, and affected cats show a characteristic gait of wide-placed forelimbs and swaying pelvis.

Creatine phosphokinase activity is elevated 2 to 3 fold in affected cats. Pelvic and pectoral girdle muscles and thoraco-lumbar epaxial muscles show mild to moderate insertional activity with fibrillation potentials and positive sharp waves on EMG. However, motor nerve conduction velocities of the sciatic nerves are normal (He et al., 2005).

Pathology: Affected animals are deficient in LNPEP and LIX1. LNPEP is a widely distributed enzyme of the endoplasmic reticulum that processes peptides for antigen presentation. The function of LIX1 is unknown, but it is highly conserved and mostly expressed in spinal cord neurons. It is probably necessary for neuron development and maintenance(Fyfe et al., 2006).

Pathologic changes are consistent with muscle denervation, which is due to lower motor neuron loss. Histopathology on hindlimb muscle samples from affected cats shows variation in myofiber size with many angular atrophic fibers both alone and in groups. In the spinal cord, there is severe loss of ventral root axons with replacement by endoneurial connective tissue. The thickness of myelin remains normal (He et al., 2005).

Control: Maine Coon cats used for breeding should be tested for the causative mutation. Affected cats should not be bred. Carriers should only be bred to tested cats demonstrated to be noncarriers.

Breed: Maine Coon.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
LIX1 Lix1 homolog (chicken) Felis catus A1 NC_058368.1 (158695639..158633180) LIX1 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
649 Maine Coon Spinal muscular atrophy LIX1 deletion, gross (>20) Naturally occurring variant A1 a ~140 kb deletion removing exons 4-6 of LIX1 and all except exon 1 of LNPEP 2006 16899656

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.
2011 Swanson, W.F., Bateman, H.L., Newsom, J., Conforti, V.A., Herrick, J.R., Lambo, C.A., Haskins, M.E., Lyons, L.A., Kittleson, M.D., Harris, S.P., Fyfe, J.C., Magarey, G.M. :
Propagation of multiple cat hereditary disease models following assisted reproduction with frozen semen and embryos Reproduction, Fertility and Development 24:139-140 (Abstract 55), 2011.
Wakeling, E.N., Fyfe, J.C. :
Lix1 knockout mouse does not exhibit spinal muscular atrophy phenotype. J Hered :S32-9, 2011. Pubmed reference: 21846745. DOI: 10.1093/jhered/esr031.
Wakeling, E.N., Joussemet, B., Costiou, P., Fanuel, D., Moullier, P., Barkats, M., Fyfe, J.C. :
Failure of lower motor neuron radial outgrowth precedes retrograde degeneration in a feline model of SMA. J Comp Neurol :, 2011. Pubmed reference: 22120001. DOI: 10.1002/cne.23010.
2008 Parkinson, NJ., Baumer, D., Rose-Morris, A., Talbot, K. :
Candidate screening of the bovine and feline spinal muscular atrophy genes reveals no evidence for involvement in human motor neuron disorders. Neuromuscular Disorders 18:394-7, 2008. Pubmed reference: 18395445. DOI: 10.1016/j.nmd.2008.03.003.
2006 Fyfe, J.C., Menotti-Raymond, M., David, V.A., Brichta, L., Schäffer, A.A., Agarwala, R., Murphy, W.J., Wedemeyer, W.J., Gregory, B.L., Buzzell, B.G., Drummond, M.C., Wirth, B., O'Brien, S.J. :
An approximately 140-kb deletion associated with feline spinal muscular atrophy implies an essential LIX1 function for motor neuron survival. Genome Res 16:1084-90, 2006. Pubmed reference: 16899656. DOI: 10.1101/gr.5268806.
2005 Iannaccone, S.T. :
Feline spinal muscular atrophy. Pediatr Res 57:322-3, 2005. Pubmed reference: 15635052. DOI: 10.1203/01.PDR.0000153671.11277.83.

Edit History


  • Created by Imke Tammen2 on 19 Aug 2021
  • Changed by Imke Tammen2 on 19 Aug 2021