ZFYVE26/Spastizin and SPG11/Spatacsin encode 2 large proteins that are mutated in hereditary autosomal-recessive spastic paraplegia/paraparesis (HSP) type 15 (AR-SPG15) and type 11 (AR-SPG11), respectively.
Quantification of dysarthrοphonia in a Cypriot family with autosomal recessive hereditary spastic paraplegia associated with a homozygous SPG11 mutation.
Mutations in SPG11 account for the most common form of autosomal recessive hereditary spastic paraplegia (HSP), characterized by a gait disorder associated with various brain alterations.
Mutations in the ALS5/SPG11/KIAA1840 gene are a frequent cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and peripheral axonal neuropathy, and account for ∼ 40% of autosomal recessive juvenile amyotrophic lateral sclerosis.
Understanding the cellular functions of spatacsin will allow deciphering mechanisms of motor cortex dysfunction in autosomal-recessive hereditary spastic paraplegia.
Mutations in the SPG11 gene have been identified to be a major cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and recently also proven to be responsible for juvenile parkinsonism associated with spastic paraplegia.
Autosomal recessive hereditary spastic paraplegia with thinning of the anterior corpus callosum (ARHSP-TCC) due to mutations in SPG11 on chromosome 15q (MIM610844) is the single most common cause of ARHSP.
Autosomal recessive hereditary spastic paraplegia (AR HSP) with thin corpus callosum (TCC) is a rare neurodegenerative disorder often caused by mutations in the gene encoding for spatacsin at the SPG11 locus on chromosome 15q.
Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is genetically heterogenous and approximately 35% of patients carry mutations in either of the SPG11 or SPG15 genes.
This study confirms the frequent occurrence of Spatacsin mutations in complex ARHSP with genotype phenotype effects and exposes the spectrum of clinical heterogeneity in SPG11.
We conclude that mutations on KIAA1840 are frequent in complex autosomal recessive hereditary spastic paraplegia but an infrequent cause of sporadic complex hereditary spastic paraplegia.
Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is a common and clinically distinct form of familial spastic paraplegia that is linked to the SPG11 locus on chromosome 15 in most affected families.