Frequency of the Allelic Variant of the PTPLA Gene Responsible for Centronuclear Myopathy in Labrador Retriever Dogs as Assessed in Italy

Abstract

Abstract. Centronuclear myopathy (CNM) is an autosomal recessive hereditary disease affecting Labrador Retriever dogs. The disease is characterized by muscle lesions, typically encompassing reduction in the number and atrophy of type II fibers, and is caused by a short interspersed repeat element insertion in exon 2 of the protein tyrosine phosphatase-like member A. The actual allele frequency is unknown; a study was undertaken to ascertain it using a convenience-sample population composed of 217 Labrador Retrievers. In addition to 3 subjects already diagnosed with CNM, used as positive controls for polymerase chain reaction, only 2 unrelated dogs were heterozygous wild-type/mutation (wild-type/mut). Thus, the frequency of the CNM allele observed in the present study was 1.8% and 0.47% when including and excluding the 3 mut/ mut homozygous cases, respectively. Based on the Hardy-Weinberg exact test (P 5 1.00), the genotype frequency without the CNM-affected dogs was in agreement with the Hardy-Weinberg equilibrium. Assuming the Hardy-Weinberg equilibrium law, the expected frequency of the homozygous mutated genotype was calculated to be approximately 0.00005, which corresponds to 1 case of CNM out of 20,000 dogs. In conclusion, the present study indicates that the CNM allele is present but rare in a convenience sample of Labrador Retrievers in Italy.

Frequentieschatting van ziekteveroorzakende mutaties in de Belgische populatie van enkele hondenrassen: Deel 2: retrievers en andere rastypes

“…The mutation probably originated in the UK and got spread to many other countries in the world (Maurer et al, 2012); however, as the results of the present study indicate, the mutation spread much less or only recently to the Belgian population. In line with the present results, Gentilini et al (2011) estimated a low frequency of 0.5% in Italy. Despite the low mutant allele frequency in Belgium, the authors advise to test Labrador retrievers for CNM, especially when they have ties to the UK population.…”

X‐linked myotubular myopathy associated with an MTM1 variant in a Maine coon cat

“…X-linked myotubular myopathy and CNM have been extensively described in both humans and dogs, with the Labrador retriever serving as a valuable model for the human disease for decades. 2,[17][18][19][20][21][22][23][24][25] The condition also has been reported in other dog breeds (including Boykin spaniels, Great Danes, Rottweilers, and a Border collie), an Arabian-cross foal, and Japanese Black calves. 4,7,8,26,27 The main differential diagnosis initially considered given the clinical presentation, age of onset, and signalment was SMA, which has been well-described in Maine coon cats.…”

“…This case represents the first report of a gene variant likely resulting in XLMTM in cats. X‐linked myotubular myopathy and CNM have been extensively described in both humans and dogs, with the Labrador retriever serving as a valuable model for the human disease for decades 2,17‐25 . The condition also has been reported in other dog breeds (including Boykin spaniels, Great Danes, Rottweilers, and a Border collie), an Arabian‐cross foal, and Japanese Black calves 4,7,8,26,27 …”

Noninvasive Assessment of Neuromuscular Disease in Dogs: Use of the 6‐minute Walk Test to Assess Submaximal Exercise Tolerance in Dogs with Centronuclear Myopathy

“…C anine centronuclear myopathies (CNM) occur primarily in the Labrador retriever breed, and are inherited either as an autosomal recessive trait with full penetrance or as an X-linked condition. [1][2][3][4][5][6] As with most neuromuscular diseases in dogs, paresis is the primary clinical manifestation of CNM. Clinical signs develop within the first 1-7 months of life, and are characterized by generalized weakness and exercise intolerance, generalized muscle atrophy, and abnormal spinal reflexes.…”

“…Canine centronuclear myopathies (CNM) occur primarily in the Labrador retriever breed, and are inherited either as an autosomal recessive trait with full penetrance or as an X‐linked condition . As with most neuromuscular diseases in dogs, paresis is the primary clinical manifestation of CNM.…”