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SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V
Author(s) -
SánchezFerrero E,
Coto E,
Beetz C,
Gámez J,
Corao AI,
Díaz M,
Esteban J,
del Castillo E,
Moris G,
Infante J,
Menéndez M,
PascualPascual SI,
López de Munaín A,
GarciaBarcina MJ,
Alvarez V
Publication year - 2013
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2012.01896.x
Subject(s) - hereditary spastic paraplegia , genetics , mutation , spastic , paraplegia , medicine , cohort , gene , genetic testing , phenotype , biology , physical therapy , cerebral palsy , psychiatry , spinal cord
Sánchez‐Ferrero E, Coto E, Beetz C, Gámez J, Corao A, Díaz M, Esteban J, del Castillo E, Moris G, Infante J, Menéndez M, Pascual‐Pascual SI, López de Munaín A, Garcia‐Barcina MJ, Alvarez V on behalf of the Genetics of Spastic Paraplegia study group. SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V. 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.