Genetic basis - Caused by a homozygous nonsense mutation in the LAMA2 gene. The mutation identified is c.3285G>A, which produces a premature stop codon (p.Trp1095*), truncating the laminin α2 protein. Laminin α2 is a vital part of the basal lamina structure in skeletal muscles; deficiency results in muscle fiber instability. It is inherited in an autosomal recessive manner.
Pathophysiology - Loss of functional laminin α2 leads to disrupted muscle fiber integrity. Results in progressive muscle wasting, atrophy, fibrosis, and weakness. Affected puppies show clinical signs by a few months of age. Elevated serum creatine kinase (CK) levels indicate muscle damage. Muscle biopsies reveal dystrophic features including fiber size variability and endomysial fibrosis. Immunofluorescent staining confirms laminin α2 deficiency.
Clinical Signs - Onset usually before 4 months of age. Poorly coordinated, short-strided gait. Generalized muscle atrophy and weakness. Exercise intolerance. Poor growth and occasional vomiting. Normal cognitive function but physical disability progresses. Possible spinal deformities and joint contractures due to muscle weakness.
Why This Matters to Breeders and Vets - Breeders: Genetic testing for the LAMA2 mutation is essential to identify carriers and reduce risk of producing affected puppies. Vets: Early clinical recognition and genetic confirmation help with diagnosis and management of affected dogs, including avoiding unnecessary treatments.