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 Silvestri, Alessandro 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
Hum. Mutat.. 2009-03-01; 30(3): E500-E519
DOI: 10.1002/humu.20945


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1. Hum Mutat. 2009 Mar;30(3):E500-19. doi: 10.1002/humu.20945.

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

Denora PS(1), Schlesinger D, Casali C, Kok F, Tessa A, Boukhris A, Azzedine H,
Dotti MT, Bruno C, Truchetto J, Biancheri R, Fedirko E, Di Rocco M, Bueno C,
Malandrini A, Battini R, Sickl E, de Leva MF, Boespflug-Tanguy O, Silvestri G,
Simonati A, Said E, Ferbert A, Criscuolo C, Heinimann K, Modoni A, Weber P,
Palmeri S, Plasilova M, Pauri F, Cassandrini D, Battisti C, Pini A, Tosetti M,
Hauser E, Masciullo M, Di Fabio R, Piccolo F, Denis E, Cioni G, Massa R, Della
Giustina E, Calabrese O, Melone MA, De Michele G, Federico A, Bertini E, Durr A,
Brockmann K, van der Knaap MS, Zatz M, Filla A, Brice A, Stevanin G, Santorelli
FM.

Author information:
(1)INSERM, UMR_S679, Paris, France .

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.

2008 Wiley-Liss, Inc.

DOI: 10.1002/humu.20945
PMID: 19105190 [Indexed for MEDLINE]

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