Limb Girdle Muscular Dystrophy Type 2S (LGMD2S) via the TRAPPC11 Gene

Limb girdle muscular dystrophy (LGMD) is a descriptive term for a group of disorders with atrophy and weakness of proximal girdle muscles and typical sparing of the heart and bulbar muscles. Clinical severity, age of onset, and disease progression are highly variable among the subtypes (Saenz et al. 2005). Serum creatine kinase levels are typically elevated, and muscle biopsies demonstrate a dystrophic process. For a comprehensive review see Pegoraro and Hoffman (2012).

Limb girdle muscular dystrophy type 2S (LGMD2S, OMIM 615356) has been described in a small number of patients demonstrating variable clinical features (Bögershausen et al. 2013). In one family, onset of symptoms occured in early childhood and included proximal weakness leading to impaired ambulation, and muscle pain and cramping.  Weakness was more pronounced in the hip girdle than shoulder girdle. Scoliosis and hip dysplasia were also present in the affected individuals.     

Affected members from two other families, both sharing a common ancestor, displayed a more complex phenotype involving both muscle and movement disorders  (Bögershausen et al. 2013). These subjects displayed mild muscle weakness, choreiform movements, truncal ataxia, and seizures. They also had global developmental delay, mild to moderate intellectual disability, and approximately half of the individuals had mild cerebellar atrophy.    

Affected individuals from all families had mildly elevated serum CpK. 

Limb girdle muscular dystrophy type 2S (LGMD2S, OMIM 615356) is inherited as an autosomal recessive disorder. A small number of cases, and only two mutations (one missense and one splicing) of the TRAPPC11 gene (OMIM 614138), have been reported to date (http://www.LOVD.nl/TRAPPC11). The TRAPPC11 protein is a component of a larger complex involved with intracellular vesicle trafficking.

Too few cases of LGMD2S have been reported to estimate clinical or analytical sensitivity.

This test provides full coverage of all coding exons of the TRAPPC11 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).