title: A new locus (SPG47) maps to 1p13.2-1p12 in an Arabic family with complicated autosomal recessive hereditary spastic paraplegia and thin corpus callosum.
abstract: The hereditary spastic paraplegias (HSP) are a heterogeneous group of genetic neurodegenerative disorders in which the main feature is progressive spasticity of the lower limbs due to pyramidal tract dysfunction. Clinically HSP are divided into two forms: a pure form that presents with progressive lower limb spasticity and weakness, sensory signs and bladder dysfunction, and a complicated form, associated with more extensive neurological and extra neurological signs as well as pathological findings on brain imaging. The clinical variability observed in HSP is supported by the large underlying genetic heterogeneity. Hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is a frequent subtype of complicated HSP clinically characterized by a slowly progressive spastic paraparesis with cognitive impairment and thin corpus callosum (TCC). SPG11, the most frequent gene associated with HSP-TCC, encodes spatacsin, a protein of unknown function. We describe two siblings from an Arabic consanguineous family with slowly progressive spastic paraparesis, mental retardation, seizures, thin corpus callosum and periventricular white matter abnormalities. Homozygosity mapping identified a novel single candidate region of 7.3 Mb on chromosome 1p13.2-1p12. The finding of a new locus for AR-HSP-TCC further demonstrates the extensive genetic heterogeneity of this condition.
authors: Pediatric Neurology Unit, Wolfson Medical Center, Holon, Sackler School of Medicine, Tel- Aviv University, Israel.
authors: Lubov
authors: L
authors: Blumkin
authors: Tally
authors: T
authors: Lerman-Sagie
authors: Dorit
authors: D
authors: Lev
authors: Keren
authors: K
authors: Yosovich
authors: Esther
authors: E
authors: Leshinsky-Silver
mesh_terms: D018912:Arabs / Q000235:genetics; D002675:Child, Preschool; D002874:Chromosome Mapping / Q000379:methods; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D003337:Corpus Callosum / Q000473:pathology*; D005260:Female; D018740:Genetic Heterogeneity; D056426:Genetic Loci / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D015419:Spastic Paraplegia, Hereditary / Q000208:ethnology / Q000235:genetics* / Q000473:pathology*
chemical_list: D011506:Proteins; C520412:SPG11 protein, human