Hereditary spastic paraplegia with mental impairment and thin corpus callosum in Tunisia: SPG11, SPG15, and further genetic heterogeneity.
Arch Neurol. 2008-03-01; 65(3):
DOI: 10.1001/archneur.65.3.393
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1. Arch Neurol. 2008 Mar;65(3):393-402. doi: 10.1001/archneur.65.3.393.
Hereditary spastic paraplegia with mental impairment and thin corpus callosum in
Tunisia: SPG11, SPG15, and further genetic heterogeneity.
Boukhris A(1), Stevanin G, Feki I, Denis E, Elleuch N, Miladi MI, Truchetto J,
Denora P, Belal S, Mhiri C, Brice A.
Author information:
(1)Department of Neurology, Habib Bourguiba University Hospital, Tunis, Tunisia.
OBJECTIVE: To perform a clinical and genetic study of Tunisian families with
autosomal recessive (AR) hereditary spastic paraplegia with thin corpus callosum
(HSP-TCC).
DESIGN: Linkage studies and mutation screening.
SETTING: Reference Center for Neurogenetics in South and Center Tunisia.
PARTICIPANTS: Seventy-three subjects from 33 « apparently » unrelated Tunisian
families with AR HSP.
MAIN OUTCOME MEASURES: 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.
DOI: 10.1001/archneur.65.3.393
PMID: 18332254 [Indexed for MEDLINE]