A novel homozygous variant in ATL1 associated with early onset spastic paraplegia 3A: Further evidence for autosomal recessive inheritance

Abstract

AbstractSpastic paraplegia 3A (SPG3A) has long been considered as an autosomal dominant disorder till the report in 2014 and 2016 of two consanguineous Arabic families, showing that ATL1 mutations may cause autosomal recessive paraplegia. Here, a third report of a consanguineous Arabic family with recessive SPG3A is described. Exome sequencing reveals homozygosity for a novel likely pathogenic ATL1 splice donor variant (c.522+1G>T) in an affected 5‐year‐old infant whereas the parents, heterozygous carriers, are asymptomatic. The infant's phenotype is consistent with an early onset complicated SPG3A with severe progressive spasticity of the lower limbs and intellectual disability.