Categories: Nervous system phene

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

Links to MONDO diseases: No links.

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).

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

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 (Cat) (VBO_0100154).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene: