Congenital muscular dystrophy in a dog with a LAMA2 gene deletion

Abstract

A 2-year-old female spayed dog was presented with a chronic history of short-strided gait and inability to completely open the jaw. Clinical signs were present since the dog was adopted from a humane society at a few months of age. Serum creatine kinase activity was abnormally high. Neurological examination, electromyography, muscle biopsies with immunofluorescent staining, and whole genome sequencing (WGS) were performed. A dystrophic phenotype was identified histologically in muscle biopsies, deficiency of laminin α2 protein was confirmed by immunofluorescent staining, and a deletion in the LAMA2 gene was identified by analysis of the WGS data. Congenital muscular dystrophy associated with a disease variant in LAMA2 was identified.

Keywords: laminin α2; muscle; myopathy; whole genome sequencing.

FIGURE 1

(A) Two‐year‐old female spayed dog with progressive history of muscle atrophy and stiff‐stilted gait. (B) Muscle histopathology showed excessive variability in myofiber size and endomysial fibrosis consistent with a dystrophic phenotype. (C) Immunofluorescent staining of muscle cryosections from the affected dog shows an absence of staining for laminin α2 and normal staining for laminin γ1 and collagen VI. These findings confirm the dystrophy is associated with laminin α2 deficiency

FIGURE 2

LAMA2 deletion detected with whole genome sequencing. A 3957 bp segment flanking the 67 735 500 bp position on canine chromosome 1 is shown. Whole genome sequence reads obtained from a normal dog (upper set) and the case (lower set) were aligned to the CanFam3.1 reference genome. Each sequence read that aligns to this region is depicted as a short gray bar (the length of each gray bar is approximately 100 bp) and the sum of reads over any given bp is indicated by the “gray wave” above each dog's set of mapped reads. The absence of any reads aligning to the approximate 67 734 500 to 67 736 500 interval signifies the deletion of that segment in the case dog's genomic DNA. The position of the 180 bp exon 5 in the reference sequence is indicated by the blue box on the bottom