A novel missense mutation confirms ATL3 as a gene for hereditary sensory neuropathy type 1

Sir, We read with great interest the article by Kornak et al. (2014) reporting a novel gene in a family with autosomal dominant sensory neuropathy complicated by acro-mutilations and bone destruction. Whole exome sequencing identified a heterozygous missense mutation (c.575A>G; p.Tyr192Cys) in atlastin 3 ( ATL3 ) which was confirmed in all affected individuals by conventional Sanger sequencing. Screening a cohort of 115 further patients exhibiting a similar phenotype detected the same variant in an additional hereditary sensory neuropathy type 1 (HSN1) family. This, together with functional data suggesting a dominant negative effect of the mutation, strongly supported the assumption that particular mutations in ATL3 result in an HSN1 phenotype. Although ATL3 is strongly expressed in the CNS and mutations in ATL1, a GTPase of similar function, is known to cause both hereditary …