Mutational spectrum of the SPG4 (SPAST) and SPG3A (ATL1) genes in Spanish patients with hereditary spastic paraplegia.
Data(s) |
07/10/2013
07/10/2013
08/10/2010
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Resumo |
BACKGROUND Hereditary Spastic Paraplegias (HSP) are characterized by progressive spasticity and weakness of the lower limbs. At least 45 loci have been identified in families with autosomal dominant (AD), autosomal recessive (AR), or X-linked hereditary patterns. Mutations in the SPAST (SPG4) and ATL1 (SPG3A) genes would account for about 50% of the ADHSP cases. METHODS We defined the SPAST and ATL1 mutational spectrum in a total of 370 unrelated HSP index cases from Spain (83% with a pure phenotype). RESULTS We found 50 SPAST mutations (including two large deletions) in 54 patients and 7 ATL1 mutations in 11 patients. A total of 33 of the SPAST and 3 of the ATL1 were new mutations. A total of 141 (31%) were familial cases, and we found a higher frequency of mutation carriers among these compared to apparently sporadic cases (38% vs. 5%). Five of the SPAST mutations were predicted to affect the pre-mRNA splicing, and in 4 of them we demonstrated this effect at the cDNA level. In addition to large deletions, splicing, frameshifting, and missense mutations, we also found a nucleotide change in the stop codon that would result in a larger ORF. CONCLUSIONS In a large cohort of Spanish patients with spastic paraplegia, SPAST and ATL1 mutations were found in 15% of the cases. These mutations were more frequent in familial cases (compared to sporadic), and were associated with heterogeneous clinical manifestations. Journal Article; Research Support, Non-U.S. Gov't; This work was supported by grants from Spanish Fondo de Investigaciones Sanitarias PI08/0915(European FEDER founds). |
Identificador |
Alvarez V, Sánchez-Ferrero E, Beetz C, Díaz M, Alonso B, Corao AI, et al. Mutational spectrum of the SPG4 (SPAST) and SPG3A (ATL1) genes in Spanish patients with hereditary spastic paraplegia. BMC Neurol. 2010; 10:89 1471-2377 (Online) PMC2964648 http://hdl.handle.net/10668/1315 20932283 |
Idioma(s) |
en |
Publicador |
BioMed Central |
Relação |
BMC neurology http://www.biomedcentral.com/1471-2377/10/89/abstract |
Direitos |
Acceso abierto |
Palavras-Chave | #Análisis de mutaciones del ADN #GTP fosfohidrolasas #Proteínas de unión al GTP #Genotipo #Paraplejía espástica hereditaria #Adenosina trifosfatasas #Medical Subject Headings::Named Groups::Persons::Age Groups::Adolescent #Medical Subject Headings::Named Groups::Persons::Age Groups::Adult #Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Aged #Medical Subject Headings::Named Groups::Persons::Age Groups::Child #Medical Subject Headings::Named Groups::Persons::Age Groups::Child::Child, Preschool #Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis, DNA::DNA Mutational Analysis #Medical Subject Headings::Named Groups::Persons::Population Groups::Continental Population Groups::European Continental Ancestry Group #Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Acid Anhydride Hydrolases::GTP Phosphohydrolases #Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Acid Anhydride Hydrolases::GTP Phosphohydrolases::GTP-Binding Proteins #Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype #Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans #Medical Subject Headings::Named Groups::Persons::Age Groups::Infant #Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins #Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle Aged #Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Pedigree #Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Phenotype #Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction #Medical Subject Headings::Diseases::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Congenital Abnormalities::Nervous System Malformations::Hereditary Sensory and Motor Neuropathy::Spastic Paraplegia, Hereditary #Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Young Adult #Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Acid Anhydride Hydrolases::Adenosine Triphosphatases |
Tipo |
info:eu-repo/semantics/article info:eu-repo/semantics/published Artículo |