Abstract
Hereditary spastic paraplegias (HSP) are a heterogeneous group of neurodegenerative disorders leading to progressive spasticity of the lower limbs. Here, we describe clinical and genetic features in an Italian family affected by autosomal recessive HSP (ARHSP) with mental impairment and thin corpus callosum (TCC). In both affected subjects, genetic analysis revealed the presence of a homozygous small deletion (733_734delAT) leading to a frameshift (M245VfsX) within the coding region of SPG11 gene, encoding spatacsin. This finding is the first independent confirmation that spatacsin loss of function mutations cause ARHPS-TCC.
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Acknowledgements
The authors are grateful to the patients and family members for their kind cooperation in this study. This work was supported by research grants to S.C. and N.B. from MIUR (Ministero Istruzione Università e Ricerca Scientifica) PRIN 2006 “Molecular pathogenesis of the motoneuron disorders as a tool for the identification of novel biomolecular and cellular therapeutic targets” and by a grant to G.P.C. from Italian Ministry of Health, “Progetti di Ricerca ex. Art. 56, 2005.” “The motor neuron disease: molecular and cellular pathways in neuronal and muscular degeneration as a cause of clinical and genetic heterogeneity.” The work of G.S. was supported by a “Groupement d’Intéret Scientifique, France” grant. We thank Prof. Alexis Brice for critical reading of the manuscript. We wish to thank the “Associazione Amici del Centro Dino Ferrari” for their support.
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Roberto Del Bo and Alessio Di Fonzo, These two authors equally contributed to the present work.
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Del Bo, R., Di Fonzo, A., Ghezzi, S. et al. SPG11: a consistent clinical phenotype in a family with homozygous Spatacsin truncating mutation. Neurogenetics 8, 301–305 (2007). https://doi.org/10.1007/s10048-007-0095-z
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DOI: https://doi.org/10.1007/s10048-007-0095-z