Hereditary spastic paraplegia

Kjellin syndrome, first described in Sweden by Kjellin in 1959, is a hereditary neuro-ophthalmologic syndrome characterized by spastic paraplegia , dementia, dysarthia and corpus callosum atrophy with a dystrophy of the posterior pole of the ocular fundus.

We report the use of Preimplantation Genetic Diagnosis (PGD) combined with parental and affected child genetic analysis to identify embryo genotype in a case of discordant parental haplotype and variable expression for Hereditary Spastic Paraplegia (HSP) mutation. The couple presented to care following referral from genetics secondary to their first child being diagnosed with early onset SPG4 hereditary spastic paraplegia. Genetic testing was performed on both intended parents as well as the affected child. Sequencing of the paternal SPAST gene revealed an R460C mutation and maternal genetic sequencing revealed a Q490P variant in the SPAST gene. Testing of the affected child revealed the presence of both maternal and paternal SPAST gene mutations as well as a de novo E39K variant in the ATF2 Gene. The couple underwent In Vitro Fertilization (IVF) treatment with trophectoderm biopsy for preimplantation genetic diagnosis. Biopsy results revealed presence of homozygous disease and presence of maternal and paternal mutant haplotypes in selected embryos making them unsuitable for transfer. The remaining embryo had only a maternal mutant haplotype of the SPAST gene present with a normal paternal haplotype. We describe the first case of ATF2 gene mutation in SPAST as a potential phenotypic modifier and/or causative mutation in HSP that may be contributing to early onset of disease. Using PGD, an unaffected embryo was transferred resulting successful delivery at term of a currently unaffected child.

Mmutations in paraplegin, a putative mitochondrial metallopeptidase of the AAA family, cause an autosomal recessive form of hereditary spastic paraplegia (HSP). Here, we analyze the function of paraplegin at the cellular level and characterize the phenotypic defects of HSP patients' cells lacking this protein. We demonstrate that paraplegin coassembles with a homologous protein, AFG3L2, in the mitochondrial inner membrane. These two proteins form a high molecular mass complex, which we show to be aberrant in HSP fibroblasts. The loss of this complex causes a reduced complex I activity in mitochondria and an increased sensitivity to oxidant stress, which can both be rescued by exogenous expression of wild-type paraplegin. Furthermore, complementation studies in yeast demonstrate functional conservation of the human paraplegin–AFG3L2 complex with the yeast m-AAA protease and assign proteolytic activity to this structure. These results shed new light on the molecular pathogenesis o...

Background and purpose: Hereditary spastic paraplegia (HSP) is a genetic disorder characterised by progressive weakness and spasticity of the lower limbs. To date, the structured rehabilitation programme for the patient with HSP is not documented. The objective of the study is to illustrate the effectiveness of the structured 8-week intensive rehabilitation programme (SEIRP). Case description: Two middle aged adult patients with HSP were included in this case reports. Both of them were brothers and sisters and classified under pure HSP type. Case 1 was a 45-year old with equinovarus deformity, paraparesis and severe spasticity. Case 2 was a 43-year old female presented with toe walking on left due to severe spasticity and hyperreflexia of the lower limbs. Interventions: The participants were given intensive physiotherapy programme which includes, stretching, strengthening and functional exercise program for the period of 8 weeks. Each treatment sessions lasted for about 60-90 minute...

Oxidative stress resulting from increased free radical production and/or defects in antioxidant defences may be the cause of various neurodegenerative disorders. In this study, the roles of oxygen free radicals, nitric oxide, superoxide dismutase, vitamin E and vitamin C were investigated in pure and complicated hereditary spastic paraparesis (HSP) patients. The results showed that plasma SOD, vitamin E and nitric oxide levels were significantly low in HSP patients. These findings indicate the influence of oxidative damage in the degenerative process of HSP.

Hereditary Spastic Paraplegias (HSPs) are heterogeneous neurodegenerative disorders whose etiopathogenesis is still unclear. The identification of pathogenic mutations in a gene (SPG7) encoding a mitochondrial metalloprotease suggested that oxidative phosphorylation (OXPHOS) alterations might underlie HSP in a subgroup of patients. We performed clinical, morphological, biochemical, and molecular genetic studies in six HSP patients and in six sporadic patients to investigate

We studied 20 Mediterranean families (40 pa-tients) with autosomal recessive hereditary spastic paraplegia and thin corpus callosum (ARHSP-TCC, MIM 604360) to characterize their clinical and genetic features. In six families (17 patients) of Algerian Italian, Moroccan, ...

Hereditary spastic paraplegia describes a diverse group of disorders characterized by progressive paraparesis primarily affecting lower limbs. In Troyer syndrome, an autosomal recessive form of hereditary spastic paraplegia, patients have dysarthria, distal amyotrophy, developmental delay and short stature in addition to spastic paraparesis. It is caused by a frameshift mutation (1110delA) in SPG20 leading to premature truncation of spartin, a protein with no known function. The objective of this study was to determine the subcellular localization of spartin and investigate the effect of the 1110delA mutation. We observed cytoplasmic expression of spartin in all transfected cell lines. Using superimposed organelle markers or immunocytochemistry staining, we established that spartin localizes to mitochondria and that this localization is dependent on sequences in the C-terminal region. Mutant spartin containing the 1110delA mutation has lost mitochondrial localization. Immunocytochem...