Tunisian hereditary spastic paraplegias: clinical variability supported by genetic heterogeneity.

A Boukhris, G Stevanin, I Feki, P Denora, N Elleuch, MI Miladi, C Goizet, J Truchetto, S Belal, A Brice, C Mhiri
Clinical Genetics. 2009-06-01; 75(6): 527-536
DOI: 10.1111/j.1399-0004.2009.01176.x

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1. Clin Genet. 2009 Jun;75(6):527-36. doi: 10.1111/j.1399-0004.2009.01176.x. Epub
2009 May 5.

Tunisian hereditary spastic paraplegias: clinical variability supported by
genetic heterogeneity.

Boukhris A(1), Stevanin G, Feki I, Denora P, Elleuch N, Miladi MI, Goizet C,
Truchetto J, Belal S, Brice A, Mhiri C.

Author information:
(1)Department of Neurology, Habib Bourguiba University Hospital, Sfax, Tunisia.

Hereditary spastic paraplegias (HSP) constitute a clinically and genetically
heterogeneous group of neurodegenerative disorders characterized by slowly
progressive spasticity of the lower extremities. We performed the first clinical,
epidemiological and genetic study of HSP in Southern Tunisia. We investigated 88
patients belonging to 38 unrelated Tunisian HSP families. We could establish the
minimal prevalence of HSP in the district of Sfax at 5.75/100,000. Thirty-one
percent of the families had a pure HSP, whereas 69% had a complicated form. The
mode of inheritance was almost exclusively compatible with an autosomal recessive
trait (97%, 37/38). Taking into account previously published results and new data
generated in this work, genetic studies revealed significant or putative linkage
to known HSP loci in 13 families (34.2%) to either SPG11 (7/38, 18.4%), SPG15
(4/38, 10.5%) or to SPG4 and SPG5 in one family each. The linkage results could
be validated through the identification of two recurrent truncating mutations
(R2034X and M245VfsX246) in the SPG11 gene, three different mutations (Q493X,
F683LfsX685 and the novel S2004T/r.?) in the SPG15 gene, the recurrent R499C
mutation in the SPG4 gene as well as the new R112X mutation in the SPG5 gene.
SPG11 and SPG15 are the major responsible HSP genes in Tunisia.

DOI: 10.1111/j.1399-0004.2009.01176.x
PMID: 19438933 [Indexed for MEDLINE]

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