SETX gene mutation in a family diagnosed autosomal dominant proximal spinal muscular atrophy

Autosomal dominant proximal spinal muscular atrophy (ADSMA) is a rare disorder with unknown gene defects in the majority of families. Here we describe a family where the diagnosis of juvenile and adult onset ADSMA was made in three individuals. Because of retained tendon reflexes an atypical course of juvenile amyotrophic lateral sclerosis (ALS4) was considered. SETX gene sequencing revealed the previously reported heterozygous missense mutation c.1166T < C, L389S in the patients. Moreover the index patient and his sister had an earlier age at onset (10 and 15 years) and a more pronounced weakness as compared to their father with an age at onset of 35 years. Both sibs additionally carried a second SETX missense mutation of unknown function V891A in trans. Altogether these results expand the phenotype associated with SETX mutations supporting the notion that patients with ADSMA should be investigated for SETX mutations.