title: Homozygous mutation in Atlastin GTPase 1 causes recessive hereditary spastic paraplegia.
abstract: 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.
authors.affiliation: Institute of Human Genetics, University Hospital Cologne, Cologne, Germany.|Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Willkomm
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.
authors.forename: Raul
authors.initials: R
authors.lastname: Heredia
authors.affiliation: Institute of Human Genetics, Martin-Luther-University Halle-Wittenberg, Halle an der Saale, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Hoffmann
authors.affiliation: Institute of Human Genetics, University Hospital Cologne, Cologne, Germany.|Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
authors.forename: Haicui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Myology, Pierre and Marie Curie University, UPMC-INSERM UMR 974, Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Voit
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Hoffman
authors.affiliation: Institute of Human Genetics, University Hospital Cologne, Cologne, Germany.|Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.|Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.|Department of Peadiatrics, University Hospital Cologne, Cologne, Germany.
authors.forename: Sebahattin
authors.initials: S
authors.lastname: Cirak
mesh_terms: D000293:Adolescent; D000483:Alleles; D019943:Amino Acid Substitution; D002648:Child; D003241:Consanguinity; D004252:DNA Mutational Analysis; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008958:Models, Molecular; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011487:Protein Conformation; D035781:Siblings; D015419:Spastic Paraplegia, Hereditary / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C440006:ATL1 protein, human; D019204:GTP-Binding Proteins