Mutations of the SPG11 gene in patients with autosomal recessive spastic paraparesis and thin corpus callosum

Hereditary spastic paraparesis (HSP) with thin corpus callosum (TCC) is a rare autosomal recessive form of complicated HSP (ARHSP-TCC). The clinical phenotype is characterised by slowly progressive spastic paraparesis and cognitive impairment which usually occurs during the second decade of life.1 However, cognitive impairment is first noticeable during childhood and may precede the occurrence of leg spasticity. The symptoms progress insidiously to severe functional disability over a period of 10–20 years.2 Some affected individuals develop a pseudobulbar involvement, with dysarthria, dysphagia and upper limb spasticity. Additional manifestations include urinary incontinence, sensory deficits in the lower limbs and late distal amyotrophy. Seizures, extrapyramidal signs and cerebellar ataxia can occur occasionally. The disorder is found in several ethnic groups, including five Chinese patients with HSP-TCC reported by Tang et al in 2004.3 The SPG11 or KIAA1840 gene, which maps to chromosome 15q21.1,4 was shown to be responsible for ARHSP-TCC when it was demonstrated that individuals with the disease carried mutational changes of SPG11 that segregates with the phenotype within families.5 The gene encodes a 2443 amino acid protein, spatacsin, of unknown function. We provide genetic and phenotypic data on five patients from two Taiwanese/Chinese families with ARHSP-TCC.