Muscular dystrophy, Beckers type

 

Gene: DMD

Transmission: Chr.X linked recessive

For an X-chromosome linked recessive genetic disease, a male must have a copy of the mutation in question to be at risk of developing the disease. All affected males transmit the mutation to all females in their progeny. A female must have two copies of the mutation in question to be at risk of developing the disease. Females with a single copy of the mutation are not at risk of developing the disease, but are carrier animals that can transmit the mutation to on average one-half of their offspring.

Mutations:

Maine Coon mutation: Substitution, DMD gene; c.4186 C>T, p.(H1396Y), exon30, chr.X.

Domestic cat mutation: Substitution, DMD gene; c.8333 G>A, p.(W2778 STOP), chr.X.

Domestic cat mutation: Substitution, DMD gene; c.4849 C>T, p.(Gln161 STOP), chr.X.

Medical system: Muscular

Breeds: Domestic Cat, Japanese Domestic, Maine Coon

Age of onset of symptoms: Earlier or later in life, depending on the mutation, but progressive.

Muscular dystrophy is a disease characterized by a progressive decline and weakness of the animal’s skeletal muscles.  The DMD gene is a large gene found on the X chromosome that codes for the Dystrophin protein which is involved in muscle contraction.  Spontaneous mutations within the DMD gene can give rise to muscular dystrophy in a number of species including man, the dog and the cat.  The muscular dystrophy is characterized by progressive muscle fiber destruction with some compensatory but inadequate reconstruction, and often leads to the early death of the animal.  As the DMD gene is located on the X chromosome, the muscular dystrophy displays sex linked heredity, whereby male animals that are affected by the disease will have mothers that are carriers for the mutation in question.  Because female carriers are easily identified by their affected male offspring, the mutations within the DMD gene that give rise to muscular dystrophy tend to be self-limiting within isolated pedigrees.  If the mutation within the DMD gene causes severe loss of Dystrophin protein function, the more severe phenotype of Duchene muscular dystrophy is seen.  If the mutation within the DMD gene cause only partial loss of dystrophin protein function, the milder Beckers muscular dystrophy is seen.  It should be noted that mutations within autosomal genes can also be responsible for different forms of muscular dystrophy.

Two littermate 2 ½ year old adult male Maine Coon cross cats from a small pedigree in Germany were seen to have gait irregularities, difficulty in jumping, poor grooming, and protrusion of the tip of the tongue.  The affected cats furthermore displayed generalized muscle hypertrophy and elevated serum levels of creatine kinase.  Clinical signs were slowly progressive.  Histological sections of muscle tissue showed evidence of dystrophic myopathy, with atrophic myocytes and muscle fiber necrosis.  Molecular studies identified a mutation within the DMD gene that correlated with the affected animals.  DNA tests on other cats within the pedigree revealed a male littermate that was phenotypically and genotypically normal, a phenotypically normal female littermate that was carrier for the mutation, and a phenotypically normal mother that was carrier for the mutation.

A single 9-year-old male Japanese domestic shorthair cat presented with muscle swelling and breathing difficulties that had been evident since the age of 3 years.  Serum creatin kinase levels were elevated.  Muscle histology revealed muscle necrosis and regeneration consistent with muscular dystrophy.  Molecular studies identified a mutation coding for a premature stop within the DMD gene as the probable cause of the muscular dystrophy phenotype.

A one-year-old male domestic cat in the United Kingdom presented with progressive difficulty in walking, difficulty in eating, a thickened tongue, and a thickened and rigid neck.  Serum creatine kinase levels were elevated.  Histological examination of a muscle sample revealed a degenerative and regenerative myopathy.  Molecular studies identified a mutation resulting in a premature stop within the DMD gene.

 

References:

OMIA link: [1888-9685]

Muto H, Yu Y, Chambers JK, et al. (2024) Association of a novel dystrophin (DMD) genetic nonsense variant in a cat with X-linked muscular dystrophy with a mild clinical course. J Vet Intern Med 38(2) :1160-1166.  [pm/38415938]

Shelton GD, Tucciarone F, Guo LT et al. (2024) Precidion medicine using whole genome sequencing identifies a novel dystrophin (DMD) variant for X-linked muscular dystrophy in a cat.  J Vet Intern Med. 38(1):135-144.  [pm/38180235]

Hilton S, Christen M, Bilzer T, et al. (2023) Dystrophin (DMD) missense variant in cats with Becker-type muscular dystrophy. Int J Mol Sci 24(4):3192.  [pm/36834603]

Beckers E, Cornelis I, Bhatti SFM, et al. (2022) A nonsense variant in the DMD gene causes x-linked muscular dystrophy in the Maine Coon cat.  Animals (Basel) 12(21):2928.  [pm/36359052]

 

Contributed by: Leah Lallouz and Camille Rivest, Class of 2028, Faculty of Veterinary Medicine, University of Montreal. (Translation DWS).