SPG11 compound mutations in spastic paraparesis with thin corpus callosum
| Autor: | Jose C. Masdeu, Jose M. Vidal-Taboada, Mario Riverol, Pau Pastor, Lluis Samaranch, Maria A. Pastor, Elena Lorenzo, Jaione Irigoyen, P. de Castro |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Genetic Markers Genotype DNA Mutational Analysis Chromosome Disorders Genes Recessive Gene mutation Nervous System Malformations Corpus callosum medicine.disease_cause Corpus Callosum Frameshift mutation Gene Frequency Thalamus Intellectual Disability Spastic medicine Humans Genetic Predisposition to Disease Genetic Testing Child Radionuclide Imaging Genetics Chromosomes Human Pair 15 Mutation Haplotype Proteins Chromosome Syndrome Frontal Lobe Frontal lobe Spain Paraparesis Spastic Neurology (clinical) Agenesis of Corpus Callosum Energy Metabolism Psychology Neuroscience |
| Zdroj: | Neurology. 71:332-336 |
| ISSN: | 1526-632X 0028-3878 |
| DOI: | 10.1212/01.wnl.0000319646.23052.d1 |
| Popis: | Background: Autosomal recessive hereditary spastic paraparesis with thin corpus callosum (ARHSP-TCC) is being increasingly recognized as a variety of spastic paraplegia with mental retardation. SPG11 gene mutations have been reported to be associated with ARHSP-TCC. Methods: As an independent group, we investigated SPG11 gene involvement in four individuals not previously described with either recessive or sporadic HSP-TCC presentation. Results: Chromosome 15q13-15 segregating autosomal disease haplotypes were different across the kindreds and sequencing of SPG11 identified four novel frameshift/nonsense segregating mutations and the R2034X mutation, which were in heterozygous compound status. The affected examined had decreased thalamic and bilateral paracentral frontal lobe metabolism on 18 F-flurodeoxyglucose PET. Conclusions: Loss-of-function SPG11 mutations are the major cause of autosomal recessive hereditary spastic paraparesis with thin corpus callosum in Southern Europe, even in apparently sporadic cases. Decreased thalamic metabolism was consistently a phenotypical SPG11 mutation hallmark. |
| Databáze: | OpenAIRE |
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