Screening of ARHSP-TCC patients expands the spectrum of SPG11 mutations and includes a large scale gene deletion

Paola S. Denora, David Schlesinger, Carlo Casali, Fernando Kok, Alessandra Tessa, Amir Boukhris, Hamid Azzedine, Maria Teresa Dotti, Claudio Bruno, Jeremy Truchetto, Roberta Biancheri, Estelle Fedirko, Maja Di Rocco, Clarissa Bueno, Alessandro Malandrini, Roberta Battini, Elisabeth Sickl, Maria Fulvia De Leva, Odile Boespflug-Tanguy, Gabriella SilvestriAlessandro Simonati, Edith Said, Andreas Ferbert, Chiara Criscuolo, Karl Heinimann, Anna Modoni, Peter Weber, Silvia Palmeri, Martina Plasilova, Flavia Pauri, Denise Cassandrini, Carla Battisti, Antonella Pini, Michela Tosetti, Erwin Hauser, Marcella Masciullo, Roberto Di Fabio, Francesca Piccolo, Elodie Denis, Giovanni Cioni, Roberto Massa, Elvio Della Giustina, Olga Calabrese, Marina A B Melone, Giuseppe De Michele, Antonio Federico, Enrico Bertini, Alexandra Durr, Knut Brockmann, Marjo S. Van Der Knaap, Mayana Zatz, Alessandro Filla, Alexis Brice, Giovanni Stevanin, Filippo M. Santorelli

Research output: Contribution to journalArticlepeer-review


Autosomal recessive spastic paraplegia with thinning of corpus callosum (ARHSP-TCC) is a complex form of HSP initially described in Japan but subsequently reported to have a worldwide distribution with a particular high frequency in multiple families from the Mediterranean basin. We recently showed that ARHSP-TCC is commonly associated with mutations in SPG11/KIAA1840 on chromosome 15q. We have now screened a collection of new patients mainly originating from Italy and Brazil, in order to further ascertain the spectrum of mutations in SPG11, enlarge the ethnic origin of SPG11 patients, determine the relative frequency at the level of single Countries (i.e., Italy), and establish whether there is one or more common mutation. In 25 index cases we identified 32 mutations; 22 are novel, including 9 nonsense, 3 small deletions, 4 insertions, 1 in/del, 1 small duplication, 1 missense, 2 splice-site, and for the first time a large genomic rearrangement. This brings the total number of SPG11 mutated patients in the SPATAX collection to 111 cases in 44 families and in 17 isolated cases, from 16 Countries, all assessed using homogeneous clinical criteria. While expanding the spectrum of mutations in SPG11, this larger series also corroborated the notion that even within apparently homogeneous population a molecular diagnosis cannot be achieved without full gene sequencing.

Original languageEnglish
JournalHuman Mutation
Issue number3
Publication statusPublished - Mar 2009


  • Mutation screening
  • SPG11
  • TCC

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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