Research on clinical and molecular genetics of hereditary spastic paraplegia 11 patients in China / 中南大学学报(医学版)

The hereditary spastic paraplegia (HSP) is a rare hereditary disease in nervous system due to the damage of corticospinal tract. HSP has various inheritance modes, including autosomal dominant inheritance, autosomal recessive inheritance, X-linked inheritance, and mitochondrial inheritance in some cases. At present, there are at least 80 subtypes of HSP. Hereditary spastic paraplegia type 11 (SPG11) is the most common subtype in autosomal recessive inheritance, and its pathogenic factor is KIAA1840 gene, which encodes spatacsin protein. A total of 52 SPG11 patients aged from 4-24 years old have been reported. Their initial symptoms were gait disturbance and/or mental retardation. As the disease develops, they may present with mental retardation, sphincter disturbance, decreased vision, ataxia, amyotrophy, pes arcuatus, ophthalmoplegia, peripheral neuropathy, and others. Except agenesis of the corpus callosum and periventricular white matter changes, patients might show cortical atrophy, ventricular dilation, and cerebellar atrophy, and so on. Chinese SPG11 patients manifested significant clinical and genetical heterogeneity and no obvious gender difference. Of them, 37 pathogenic mutations of KIAA1840 gene were detected, which all introduced truncated mutation of spatacsin protein. KIAA1840 gene frameshift mutation is the most common type of mutation.

Thinning of the Corpus Callosum and Cerebellar Atrophy is Correlated with Phenotypic Severity in a Family with Spastic Paraplegia Type 11

BACKGROUND: Mutations in the spatacsin gene are associated with spastic paraplegia type 11 (SPG11), which is the most-common cause of autosomal recessive hereditary spastic paraplegia. Although SPG11 has diverse phenotypes, thinning of the corpus callosum is an important feature. CASE REPORT: Clinical, genetic, and radiological evaluations were undertaken in a large family from Gujarat in North India with hereditary spastic paraplegia, whose affected members presented with varying degrees of spasticity, ataxia, and cognitive impairment. The clinical severity and the degree of corpus callosum and cerebellar atrophy varied among the four affected individuals in the family. Genetic testing of the affected members revealed recessive mutations in the spatacsin gene, consistent with a diagnosis of SPG11. CONCLUSIONS: We believe that the extent of corpus callosum thinning and cerebellar atrophy is correlated with disease severity in affected patients. The addition of extrapyramidal features in the most-affected members suggests that SPG11 exhibits considerable phenotypic heterogeneity.