title: A novel splice site mutation in ERLIN2 causes hereditary spastic paraplegia in a Saudi family.
abstract: Hereditary Spastic Paraplegias (HSP) encompass a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by insidiously progressive weakness and spasticity of the lower extremities. We describe a consanguineous Saudi family segregating a complicated form of HSP in an autosomal recessive pattern. The two affected siblings had early onset, cognitive, speech and motor involvement with spasticity of the lower extremities. Their upper extremities were mildly hypertonic. An intronic splice acceptor site mutation in ERLIN2 was found to be responsible for causing this disorder found in this family. ERLIN2 is a mediator of endoplasmic reticulum degradation pathway (ERAD) which helps to remove the aberrant proteins. Our results, in concurrence with previous studies suggest that alteration in ERLIN2 is one of the causes of complicated HSP, thereby increasing the spectrum of known mutations in SPG18.
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia. smajid@kfshrc.edu.sa
authors.forename: Salma M
authors.initials: SM
authors.lastname: Wakil
authors.forename: Saeed
authors.initials: S
authors.lastname: Bohlega
authors.forename: Samya
authors.initials: S
authors.lastname: Hagos
authors.forename: Batoul
authors.initials: B
authors.lastname: Baz
authors.forename: Haya
authors.initials: H
authors.lastname: Al Dossari
authors.forename: Khushnooda
authors.initials: K
authors.lastname: Ramzan
authors.forename: Zuhair N
authors.initials: ZN
authors.lastname: Al-Hassnan
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D003241:Consanguinity; D023061:Gene Order; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D022821:RNA Splice Sites; D012529:Saudi Arabia; D015419:Spastic Paraplegia, Hereditary / Q000175:diagnosis / Q000235:genetics*
chemical_list: C121703:ERLIN2 protein, human; D008565:Membrane Proteins; D022821:RNA Splice Sites