There are still many cases of orphan hereditary neuromuscular diseases. This results in diagnostic error that is often harmful to the care of the patient himself/herself, but also to the family (genetic consultation). In this context, the development of high throughput sequencing or next-generation sequencing (NGS) techniques represents a major contribution.
An article published in April 2021 by an international consortium that includes several members of the Institute of Myology in Paris, illustrates this perfectly. In this study, mutations in the JAG2 gene were implicated in 23 diseases belonging to 13 unrelated families. This gene is involved in the NOTCH signalling pathway. There could be, as demonstrated by functional studies supporting this study, close links to 2 other genes, MEGF10 and POGLUT-1, that are already implicated in other types of muscular dystrophy, including one type of Limb Girdle Muscular Dystrophy (LGMD), LGMD R21. Even though a “limb girdle” type pattern is, indeed, often encountered, the authors stress that the clinical phenotype is highly variable, with the age of onset ranging from early childhood to adulthood. The same applies to histological lesions. This type of muscular dystrophy seems relatively common and represents real progress for neuromuscular diseases that have not yet been elucidated. At this stage, it is not known whether the authors will succeed in having this classified as a new form of LGMD.