The description of four new French cases of Welander-type distal myopathy and 20 cases from a review of the literature confirms the digenic nature of the disease: the p.Asn357Ser mutation in the TIA1 gene is associated with four different SQSTM1 variants.
- The disease is most often asymmetric and predominantly affects the foot lifters and finger extensors.
- There was a moderate elevation of CPK and a myopathic electromyogram.
- Two patients had sensory-motor polyneuropathy and one had neuropathic abnormalities on muscle biopsy.
- Of the 18 muscle biopsies available, 44.4% showed bordered vacuoles, 16.7% myofibrillar disorganisation and 38.9% both.
A targeted search for the p.Asn357Ser mutation of the TIA1 gene in 414 patients with distal myopathies followed at the Hôpital Pitié-Salpêtrière found it in 11 cases, a prevalence of 2.7%.
- While nine of these patients did not have a definitive genetic diagnosis, one patient had, in association with the p.Asn357Ser mutation in the TIA1 gene , a probably pathogenic variant of MYH7 and a second patient had two probably pathogenic variants of the TTN gene.
- No cases of homozygous p.Asn357Ser mutations in the TIA1 gene were found.
The authors conclude that the TIA1 p.Asn357Ser variant may play a role as a genetic modifier in other distal myopathies, or even in other muscle diseases.
