Hereditary spastic paraplegia with mental impairment and thin corpus callosum in Tunisia: SPG11, SPG15, and further genetic heterogeneity.
OBJECTIVE
To perform a clinical and genetic study of Tunisian families with autosomal recessive (AR) hereditary spastic paraplegia with thin corpus callosum (HSP-TCC).


METHODS
Linkage studies and mutation screening.


METHODS
Reference Center for Neurogenetics in South and Center Tunisia.


METHODS
Seventy-three subjects from 33 "apparently" unrelated Tunisian families with AR HSP.


METHODS
Families with AR HSP-TCC were subsequently tested for linkage to the corresponding loci using microsatellite markers from the candidate intervals, followed by direct sequencing of the KIAA1840 gene in families linked to SPG11.


RESULTS
We identified 8 Tunisian families (8 of 33 [24%]), including 19 affected patients, fulfilling the clinical criteria for HSP-TCC. In 7 families, linkage to either SPG11 (62.5%) or SPG15 (25%) was suggested by haplotype reconstruction and positive logarithm of odds score values for microsatellite markers. The identification of 2 recurrent mutations (R2034X and M245VfsX) in the SPG11 gene in 5 families validated the linkage results. The neurological and radiological findings in SPG11 and SPG15 patients were relatively similar. The remaining family, characterized by an earlier age at onset and the presence of cataracts, was excluded for linkage to the 6 known loci, suggesting further genetic heterogeneity.


CONCLUSIONS
Autosomal recessive HSP-TCC is a frequent subtype of complicated HSP in Tunisia and is clinically and genetically heterogeneous. SPG11 and SPG15 are the major loci for this entity, but at least another genetic form with unique clinical features exists.
Boukhris
Amir
A
Department of Neurology, Habib Bourguiba University Hospital, Tunis, Tunisia.
Stevanin
Giovanni
G
Feki
Imed
I
Denis
Elodie
E
Elleuch
Nizar
N
Miladi
Mohamed Imed
MI
Truchetto
Jérémy
J
Denora
Paola
P
Belal
Samir
S
Mhiri
Chokri
C
Brice
Alexis
A
D000328:Adult; D061085:Agenesis of Corpus Callosum; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D018740:Genetic Heterogeneity; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D001523:Mental Disorders / Q000150:complications / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D015419:Spastic Paraplegia, Hereditary / Q000150:complications / Q000235:genetics / Q000473:pathology; D014416:Tunisia / Q000453:epidemiology
D011506:Proteins; C520412:SPG11 protein, human