Two independent international studies, published and also presented at Myology 2024, have reported the involvement of the SNUPN gene in a new form of muscular dystrophy. Like LAMA2, SNUPN is thought to be responsible for a congenital form (CMD) presenting before the age of two, and a later form which could be the 29th recessive form of LGMD (LGMD R29) identified.
Analyses of a total of 23 patients (12 females and 11 males, aged between 3 and 36 years) from 17 unrelated families on three continents, all carriers of an anomaly in the SNUPN gene, showed:
- progressive weakness of the proximal muscles of the arms and legs, often associated with distal damage, with loss of the ability to walk in more than half of cases;
- involvement mainly of the paravertebral, gluteal, quadriceps, gracilis, peroneal and gastrocnemius muscles;
- severe respiratory difficulties and significant, diffuse retractions;
- non-muscular damage in some patients, particularly to the brain (cerebellum atrophy, etc.) and eyes (cataracts);
- muscle fibres of variable size, with significant fibrosis and fatty infiltration, and the presence in some of abnormalities in the structure of the myofibrils as seen in myofibrillar myopathies;
- a generally high level of creatinine kinase in the blood.
The study of cells from patients shows disturbed nucleocytoplasmic transport and RNA maturation, and the animal model confirms the pathogenic role of SNUPN: Drosophila in which the gene has been inactivated have significantly reduced motor function and life expectancy.
