1. Hereditary Spastic Paraplegia With Mental Impairment and Thin Corpus Callosum in Tunisia
- Author
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Alexis Brice, Elodie Denis, N. Elleuch, Imed Feki, Samir Belal, Giovanni Stevanin, Mohamed Imed Miladi, Amir Boukhris, Paola S. Denora, Chokri Mhiri, Jeremy Truchetto, Department of neurology, Hopital Habib Bourguiba - Habib Bourguiba Hospital [Sfax], Neurologie et thérapeutique expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Neurology, National Institute of neurology, This work was financially supported by the French Tunisian cooperation project (Drs Briceand Mhiri) led by INSERM (France) and Direction Générale de la Recherche Scientifique et de la Rénovation Technologique (DGRSRT) (Tunisia), the VERUM Foundation (Dr Brice), the GIS (Groupement d'Inte´reˆt Scientifique)– Maladies Rares (Dr Stevanin), and the French Agency for Neuroscience Research (to the SPATAX Network and Dr Stevanin). Dr Boukhris received a fellowship from the French Association Strumpell–Lorrain., Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Aouinat, Farid
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Tunisia ,Genotype ,Hereditary spastic paraplegia ,DNA Mutational Analysis ,Neurogenetics ,Genetic Heterogeneity ,03 medical and health sciences ,0302 clinical medicine ,Arts and Humanities (miscellaneous) ,Genetic linkage ,medicine ,Humans ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,030304 developmental biology ,Family Health ,Genetics ,Linkage (software) ,0303 health sciences ,Spastic Paraplegia, Hereditary ,Genetic heterogeneity ,business.industry ,Mental Disorders ,Haplotype ,Proteins ,medicine.disease ,Magnetic Resonance Imaging ,3. Good health ,Phenotype ,Microsatellite ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Female ,Neurology (clinical) ,Agenesis of Corpus Callosum ,business ,030217 neurology & neurosurgery - Abstract
International audience; 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.
- Published
- 2008