Due to the rarity of these myopathies, if some clinical patterns (such as distal myopathy associated with cardiomyopathy due to desmin mutations) are now well known, surprises remain possible and should lead to systematic testing of the known genes in case of a typical histological presentation.
This family shows a hereditary distal myopathy with some features in common with previously-reported cases in which biopsies showed cytoplasmic inclusion bodies containing desmin.
The spectacular progress concerning dystrophin and its pathology, the dystrophinopathies, has led to a somewhat arbitrarily separated heterogeneous group of nondystrophinopathic muscular dystrophies that currently comprise the Emery-Dreifuss type, the nosologically heterogeneous autosomal-recessive limb-girdle muscular dystrophy, the severe childhood autosomal-recessive muscular dystrophy, the merosin-positive and -negative congenital muscular dystrophies, the autosomal-recessive distal muscular dystrophy of Miyoshi, the facio-scapulo-humeral muscular dystrophy, and myotonic dystrophy, both the adult and neonatal variants.
We identified a novel nonsense variant in DSG2 (c.710T > A, p.Leu237Ter) and a reported pathogenic missense variant of distal myopathy in MYH7 (c. 1322C > T, p.Thr441Met) in the proband of an ARVC pedigree.
Mutations in dysferlin and anoctamin 5 are the cause of muscular disorders, with the main presentations as limb-girdle muscular dystrophy or Miyoshi type of distal myopathy.
We speculate that dysferlin is involved in the pathogenesis of the myopathy in these patients, which may represent a new disease entity presenting as a distal myopathy.
The dysferlin gene, a strong candidate gene responsible for two other distal myopathies in the same region, is located centromeric to PAC3-H52 and can thereby formally be excluded as cause for WDM.
Mutations in dysferlin lead to Limb Girdle Muscular Dystrophy 2B (LGMD2B), Miyoshi Myopathy (MM), and Distal Myopathy with Anterior Tibialis onset (DMAT).
Dysferlin, the protein product of the gene mutated in patients with an autosomal recessive limb-girdle muscular dystrophy type 2B (LGMD2B) and a distal muscular dystrophy, Miyoshi myopathy, is homologous to a Caenorhabditis elegans spermatogenesis factor, FER-1.
The dysferlin gene, a strong candidate gene responsible for two other distal myopathies in the same region, is located centromeric to PAC3-H52 and can thereby formally be excluded as cause for WDM.
Dysferlin-deficiency due to mutations in the dysferlin gene leads to muscular dystrophy (Miyoshi myopathy (MM), limb girdle muscular dystrophy type 2B (LGMD2B), distal myopathy with anterior tibial onset (DMAT)), typically with early adult onset.
This approach may also be applicable to limb-girdle muscular dystrophy type 2B (LGMD2B), Myoshi myopathy (MM) and distal myopathy with anterior tibial onset (DMAT), which are caused by mutations in the dysferlin-encoding DYSF gene.
Recessive mutations in ANO5 cause primary skeletal muscle disorders (limb-girdle muscular dystrophy 2L and distal muscular dystrophy), which are phenotypically similar to dysferlinopathy, a muscular dystrophy due to dysferlin-encoding gene (DYSF) mutations.