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Background Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous neurodegenerative diseases characterized by progressive spasticity of the lower limbs.The various mutations occured in SPG11 gene have been recently identified causing autosomal recessive HSP with thin corpus callosum (ARHSP-TCC).Method We have performed mutation detection in 15 autosomal recessive HSP families (26 patients) and 18 sporadic cases by sequencing the PCR products spanning the exonic and intron-exon boundary regions of the gene.Result A novel compound heterozygous mutation, c.[5121_5122insAG]+[6859C>T] (p.[I1708RfsX2]+[Q2287X]), in the gene has been identified in a family from Huizhou city of Guangdong province.The genetic analyses of the family showed that the mother carried the mutation of c.[5121_5122insAG] and the father carried the c.[6859C>T] mutation.The affected son unfortunately inherited bother mutations from the parents, whereas each of his younger brother and sister only inherited one of the mutations.Clinical feature and laboratory investigations show that the son inherited the compound mutations has TCC, cognitive decline and lower motor neuron degeneration.The mothemal mutation, c.5121_5122insAG, caused the reading frame shiR through a two-base pair insertion on the splice site of exon 29.This introduced a premature stop codon at residue 1709 (p.I1708RfsX2).The paternal mutation, c.6859C>T, caused the nonsense mutation Q2287X in exon 38.Therefore, this mutation resulted in truncated protein.Both mutations were not found in control subjects.Haplotype analysis suggested that the haplotypes bearing the two mutations co-segregated with ARHSP-TCC in this family.Across species alignment showed that the two mutations occurred at the highly conserved nucleotides/amino acids.Structure modeling of the mutant proteins predicted gross changes at the second structure levels.These include the loss of 31 motives, introduction of an extra transmembrane domain, the reversal of the direction of the crossing membrane within the first transmembrane domain, and the change in the number of the α-helix and β-pleated sheet of the protein.Conclusion Our study widens the spectrum of mutation in SPG11.