SPG11 compound mutations in spastic paraparesis with thin corpus callosum.
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.
Samaranch
L
L
Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research (CIMA), Pío XII 55, 31008-Pamplona (Navarra), Spain.
Riverol
M
M
Masdeu
J C
JC
Lorenzo
E
E
Vidal-Taboada
J M
JM
Irigoyen
J
J
Pastor
M A
MA
de Castro
P
P
Pastor
P
P
D000328:Adult; D061085:Agenesis of Corpus Callosum; D002648:Child; D025063:Chromosome Disorders / Q000235:genetics; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D003337:Corpus Callosum / Q000000981:diagnostic imaging / Q000378:metabolism; D004252:DNA Mutational Analysis; D004734:Energy Metabolism / Q000235:genetics; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D005787:Gene Frequency; D005808:Genes, Recessive / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D009421:Nervous System Malformations / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D020336:Paraparesis, Spastic / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D011877:Radionuclide Imaging; D013030:Spain; D013577:Syndrome; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology
D005819:Genetic Markers; D011506:Proteins; C520412:SPG11 protein, human