title: Mental deficiency in three families with SPG4 spastic paraplegia.
abstract: Mutations and deletions in the SPG4 gene are responsible for up to 40% of autosomal dominant hereditary spastic paraplegia (HSP). Patients have pyramidal signs in the lower limbs and some present additional features including cognitive impairment such as executive dysfunction or subcortical dementia. We report 13 patients from three SPG4 families, who had spastic paraplegia associated with mental retardation (n=1), extensive social dependence (n=10), or isolated psychomotor delay (n=2). In family FSP-698, 10 affected individuals had both HSP and mental deficiency leading to social dependence in 9 and institutionalization in 5. The mean age at onset of spastic paraplegia was 11+/-20 years, ranging from 1 to 51 years. This phenotype segregated either with a novel p.Glu442Lys mutation or the two previously described p.Arg459Thr and p.Arg499Cys substitutions in the SPG4 gene. Since two of these mutations were previously reported in families with a pure form of the disease, another genetic factor linked to SPG4 could be responsible for this complex phenotype.
authors.affiliation: Department of Genetics and Cytogenetics, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Ribaï
authors.forename: Christel
authors.initials: C
authors.lastname: Depienne
authors.forename: Estelle
authors.initials: E
authors.lastname: Fedirko
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Jothy
authors.forename: Caterine
authors.initials: C
authors.lastname: Viveweger
authors.forename: Valérie
authors.initials: V
authors.lastname: Hahn-Barma
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D019943:Amino Acid Substitution; D005260:Female; D005799:Genes, Dominant; D006239:Haplotypes; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D015419:Spastic Paraplegia, Hereditary / Q000150:complications / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D000074181:Spastin
chemical_list: D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human