GNE myopathy: Characteristics of affected patients diagnosed in mainland France

GNE myopathy has been increasingly recognized over the last few years as a worldwide cause of distal myopathy. Diagnosing this disorder is now becoming crucial as treatment issues are now at stake. Beside important and well-known clusters of cases (i.e. in Japan or Israel) harboring recurrent mutations, many countries host genetically heterogeneous populations. We present here the current situation in mainland France (10 more patients have been diagnosed in the Reunion Island), where 30 patients stemming from 30 different families have been diagnosed to date. Sex ratio was 1. Sixteen patients were of European descent, the others had various origins (India, Maghreb, Mauritius, Senegal); one patient stemmed from a Jewish Karaite family. They harbored various genetic abnormalities: 2 patients had a null mutation, the other missense nucleotide substitutions. Ten patients displayed homozygous mutations, whereas the others were compound heterozygous. Several mutations were recurrent, such as p.V727M, p.M743T or p.R308. Patients presented with a distal onset in the early twenties (range: 14–40 y) and a progressive course leading to loss of ambulation within 10 to 20 years, concomitant with an upper limb involvement. Individual cases may however be more severe (one patient lost ambulation within 5 years) or more benign (a 72-year-old patient is still ambulant). Quadriceps were spared in all cases. We found no cardiac involvement in our patients. Respiratory function was moderately altered in about 20% of cases. The characteristics or French patients are in line with previously described cohorts; no genotype–phenotype correlation could be drawn.