In other species: dog , domestic cat

Categories: Muscle phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 300376 (trait) , 300377 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0010311: Becker muscular dystrophy

Mendelian trait/disorder: yes

Mode of inheritance: X-linked

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2012

Cross-species summary: Variants in the DMD gene may give rise to phenotypes with different severity. True null alleles cause the more severe Duchenne muscular dystrophy (OMIA:001081), while alleles with partial remaining protein function give rise to the milder Becker muscular dystrophy.

Species-specific name: dystrophinopathy, dystrophin insufficiency

Species-specific description: This disorder was first reported (in a single pig) by Horiuchi et al. (2014). Schwarz et al. (2021): “In Austria, routine meat inspection identified “gluteal muscles infiltrated by fat and muscle tissue obviously being replaced by fat in two different slaughter pigs. … The two muscle samples were investigated histopathologically and diagnosed with fatty muscular dystrophy. The results of routine histopathology were confirmed by dystrophin-specific immunohistochemistry. Sex of the two affected animals was determined retrospectively using a PCR-based protocol and resulted in one male and one female pig. A survey to determine the prevalence of fatty muscular disorders of pork revealed that this phenomenon gets frequently observed in Styria, but also occurs in Upper Austria and Lower Austria. Mostly gluteal and lumbal muscles were affected and approximately 20-40% of the affected muscles were replaced by fat.” A genetic cause was considered by the authors, as the disease showed similarity to Becker muscular dystrophy and the previously reported case in Japan (Horiuchi et al., 2013). Further research is required. See also OMIA:001685-9823 : Stress syndrome, DMD-related in Sus scrofa (pig)

Molecular basis: Nonneman (2012) report a dystrophin variant (omia.variant:179) causing a stress syndrome in pigs (see OMIA:001685-9823 : Stress syndrome, DMD-related in Sus scrofa (pig)). Hollinger et al. (2014) investigated the skeletal muscle phenotype in pigs with this variant and classified these pigs as "representative of a Becker phenotype". Aihara et al. (2022): "Analysis of dystrophin mRNA showed a 62 base pair insertion between exons 26 and 27. The insertion was derived from intron 26. Based on these findings, we diagnosed the case as Becker muscular dystrophy-the first known muscular dystrophy case induced by pseudoexon insertion in animals." Kamiya et al. (2003) "examined the lesions and the distribution of dystrophin expression in 25 pigs with dystrophinopathy. In addition, complementary deoxyribonucleic acid (cDNA) sequencing and western blotting were performed in 6 of the 25 cases ... . The sequence analysis of the dystrophin cDNA revealed the presence of 14 missense mutations and 3 types of shortened transcripts with exon skipping." 5 of the 14 missense mutations (based on SIFT and PolyPhen-2 scores) and 3 types of shortened transcripts generated by the skipping of exons were considered by the authors to be associated with the pathogenesis: c.1773A>G p.(Glu527Gly); c.1851T>C p.(Ile553Thr); c.6050C>T p.(Arg1953Trp) (previously reported omia.variant:179); c.7529T>C p.(Ser2446Pro); c.11118G>A p.(Ser3642Asn); c.4834_5013del; c.8185_8904del and c.[10191_10229del,10362_10520del] (cDNA coordinates based on transcript NM_001012408.1.). However, three of the six pigs presented with multiple suspected pathogenic variants. The authors concluded that the "examination of the effects of each mutation on motor function and meat quality, respectively, will require the accumulation of additional cases."

Clinical features: Aihara et al. (2022) reported "a case of Becker muscular dystrophy in a 6-month-old, mixed-breed, castrated male pig detected with macroglossia at a meat inspection center. The pig presented a severely enlarged tongue extending outside its mouth. The tongue was firm and pale with discolored muscles. Histologically, there was severe fibrosis, fatty replacement, and myofiber necrosis, degeneration, and regeneration. Immunofluorescence showed focal and severely weak labeling for dystrophin at the sarcolemma of myocytes in the tongue."

Associated gene: