A paper recently published by Madhuri Hegde, Emory University, and colleagues analyzed the outcomes of genetically sequencing a large group of patients with limb girdle weakness in the United States.
This study is unique in that it included a very large cohort of patients – 4656 – who were enrolled in the Muscular Dystrophy Association (MDA) and Jain Foundation LGMD molecular diagnostic testing programs from June 2015 to June 2017. Patients with suspected LGMD provided blood samples, which were subjected to Next Generation Sequencing of a targeted gene panel containing genes that cause LGMD, as well as genes that cause clinically similar muscular dystrophies.
Twenty seven percent of patients received a genetic diagnosis, with the most common causative LGMD genes being:
- CAPN3/LGMD2A&1I (17%)
- DYSF/LGMD2B (16%)
- FKRP/LGMD2I (9%)
- ANO5/LGMD2L (7%)
Other interesting findings include:
- Report of a new CAPN3 mutation, c.598_612del15, that appears to cause autosomal dominant calpainopathy (LGMD1I). Further studies are required to confirm the dominant inheritance of this mutation.
- 31 individuals had pathogenic mutations in more than one LGMD gene, suggesting multigenic inheritance (LGMD as a result of mutations in more than gene)