Categories: Cardiovascular system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 300377 (gene) , 302045 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: X-linked

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2012

Species-specific description: see also OMIA:001888-9823 : Muscular dystrophy, Becker type in Sus scrofa (pig)

Molecular basis: Nonneman et al. (2012) reported a GWAS in a pedigree of USMARC pigs segregating for a novel stress syndrome. The scan implicated just one region, namely chromosome "SSCX at 25.1-27.7 Mb over the dystrophin gene (DMD)". A missense mutation (R1958W) in exon 41 of the dystrophin gene appears to be the causative mutation.

Clinical features: "The symptoms included open-mouth breathing, skin discoloration, vocalization and loss of mobility . . . sometimes resulting in death, during regular processing and weighing" (Nonneman et al., 2012)

Pathology: "Affected animals had elevated plasma creatine phosphokinase (CPK) levels before and immediately after isoflurane challenge and cardiac arrhythmias. ... Histopathology of affected left ventricular cardiac tissues showed evidence of myofibrillar degeneration and necrosis .... Myocardial fibers showed loss of cross-striation, pyknotic nuclei and associated aggregation of lymphocytes. Immunoblots of heart and skeletal muscle protein from 8 week-old pigs ... showed a dramatic reduction (~50%) in dystrophin protein in affected pigs compared to normal littermates" (Nonneman et al., 2012) Hollinger et al. (2014) investigated the skeletal muscle phenotype in pigs with this variant and classified these pigs as "representative of a Becker phenotype".

Associated gene: