ABSTRACT
Mutations in the SPG7 gene were initially reported in patients with autosomal recessive hereditary spastic paraplegia (HSP). Recent works suggested a dominant effect for some SPG7 mutations. To characterize the SPG7 mutational spectrum in a large cohort of Spanish HSP patients, we sequenced the whole SPG7 gene in a total of 285 Spastic Paraplegia patients. Large gene rearrangements were also ascertained in some patients. We found a total of 14 SPG7 mutations (12 new) in 14 patients; 2 were large deletions. All the mutation carriers had an adult onset age but only five (35%) had a complicated phenotype. We identified a single mutation in 13 patients. Familial analysis suggested a dominant inheritance for one (p.Leu78*) of these mutations. Carriers of the rare p.A510V variant were significantly more frequent in patients vs healthy controls (3% vs 1%), suggesting a pathogenic role for this SPG7 variant. We reported a high frequency of patients with only one SPG7 mutation, and a putative pathogenic role for the p.A510V variant.
Subject(s)
Amino Acid Substitution , Metalloendopeptidases/genetics , Mutation , Spastic Paraplegia, Hereditary/genetics , ATPases Associated with Diverse Cellular Activities , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cohort Studies , DNA Mutational Analysis , Gene Frequency , Genes, Dominant , Genetic Predisposition to Disease , Genetic Testing , Genotype , Humans , Infant , Middle Aged , Phenotype , Spain , Spastic Paraplegia, Hereditary/diagnosis , Young AdultABSTRACT
Many reports provided strong evidence of the influence of genetic factors in the pathogenesis of psoriasis (Ps). A higher prevalence of lipid disorders in psoriatic patients has been reported. Because apolipoprotein E (apoE) is involved in lipid metabolism, APOE gene variants could be candidates to influence Ps-risk. However, data about the potential influence of the APOE genotypes in Ps are inconclusive. Our objective was to investigate the relationship between the common APOE-epsilon2/epsilon3/epsilon4 variation and Ps in a Caucasian population. Our study involved 331 unrelated Ps-patients and 400 healthy controls. Patients and controls were genotyped for the APOE-epsilon2/epsilon3/epsilon4 polymorphism, and allele and genotype frequencies were statistically compared between the two groups and between patients according to disease severity. Mean lipid values were also compared between the APOE genotypes. Allele and genotype frequencies did not differ between patients and controls. APOE-epsilon4 carriers were significantly more frequent in patients with severe Ps compared to controls (P = 0.003) and to non-severe Ps (P = 0.017). No significant difference in mean lipid values was found between the APOE genotypes. The APOE-epsilon4 allele could be a risk factor for developing a severe form of psoriasis.
