Homozygous mutation in Atlastin GTPase 1 causes recessive hereditary spastic paraplegia

Hereditary spastic paraplegia (hsp) is an extremely heterogeneous disease caused by mutations of numerous genes leading to lower limb spasticity (pure forms) that can be accompanied by neurological symptoms (complex forms). despite recent advances, many causal mutations in patients remain unknown. we identified a consanguineous family with the early-onset hsp. whole-exome sequencing revealed homozygosity for a novel atlastin gtpase 1 gene stop mutation in three affected siblings. heterozygous parents and siblings were unaffected. this was unexpected as mutations in the atlastin 1 gene are known to cause autosomal dominant hsp. but our study showed that atlastin 1 mutations may cause autosomal recessively inherited paraplegia with an underlying loss-of-function mechanism. hence, patients with recessive forms of hsp should also be tested for the atlastin 1 gene.