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: Information relating to feline spinal muscular atrophy due to likely causal variants in the LIX1 gene has been moved from the generic 'OMIA 000939-9685 : Spinal muscular atrophy in Felis catus' entry to this page [19/08/2021]

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. Disease progression slows around 4-8months and affected cats with varying severity of clinical signs lived for at least 8 years of age (He et al., 2005).

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).

[IT thanks DVM student Jacqualine Yue for suggested changes in April 2022]

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.

Peripheral nerves present with a fascicular pattern of mild nerve fiber loss with occasional small, thinly myelinated nerve fibers. Variable depletion of myelinated nerve fibers is observed in intramuscular nerve branches.

In the spinal cord, there is severe loss of large ventral root myelinated axons with replacement by endoneurial connective tissue. These findings were not present in dorsal nerve roots. Segmental demyelination was not observed in dorsal or ventral roots. (He et al., 2005).

[IT thanks DVM student Jacqualine Yue for suggested changes in April 2022]

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

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 Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
649 Maine Coon Spinal muscular atrophy LIX1 deletion, gross (>20) Naturally occurring variant Felis_catus_9.0 A1 g.161036890_161176706del published as "a ~140 kb deletion removing exons 4-6 of LIX1 and all except exon 1 of LNPEP" 2006 16899656 Genomic position in Felis_catus_9.0 is based on information provided by Leslie Lyons and Reuben Buckley.

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 :S32-39, 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 520:1737-1750, 2011. Pubmed reference: 22120001. DOI: 10.1002/cne.23010.
2008 Parkinson, N.J., 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 He, Q., Lowrie, C., Shelton, GD., Castellani, RJ., Menotti-Raymond, M., Murphy, W., O'Brien, SJ., Swanson, WF., Fyfe, JC. :
Inherited motor neuron disease in domestic cats: a model of spinal muscular atrophy. Pediatr Res 57:324-30, 2005. Pubmed reference: 15635053. DOI: 10.1203/01.PDR.0000153625.46892.6F.
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
  • Changed by Imke Tammen2 on 31 Mar 2022
  • Changed by Imke Tammen2 on 23 Apr 2022