TY - JOUR
T1 - Screening of ARHSP-TCC patients expands the spectrum of SPG11 mutations and includes a large scale gene deletion
AU - Denora, Paola S.
AU - Schlesinger, David
AU - Casali, Carlo
AU - Kok, Fernando
AU - Tessa, Alessandra
AU - Boukhris, Amir
AU - Azzedine, Hamid
AU - Dotti, Maria Teresa
AU - Bruno, Claudio
AU - Truchetto, Jeremy
AU - Biancheri, Roberta
AU - Fedirko, Estelle
AU - Di Rocco, Maja
AU - Bueno, Clarissa
AU - Malandrini, Alessandro
AU - Battini, Roberta
AU - Sickl, Elisabeth
AU - De Leva, Maria Fulvia
AU - Boespflug-Tanguy, Odile
AU - Silvestri, Gabriella
AU - Simonati, Alessandro
AU - Said, Edith
AU - Ferbert, Andreas
AU - Criscuolo, Chiara
AU - Heinimann, Karl
AU - Modoni, Anna
AU - Weber, Peter
AU - Palmeri, Silvia
AU - Plasilova, Martina
AU - Pauri, Flavia
AU - Cassandrini, Denise
AU - Battisti, Carla
AU - Pini, Antonella
AU - Tosetti, Michela
AU - Hauser, Erwin
AU - Masciullo, Marcella
AU - Di Fabio, Roberto
AU - Piccolo, Francesca
AU - Denis, Elodie
AU - Cioni, Giovanni
AU - Massa, Roberto
AU - Della Giustina, Elvio
AU - Calabrese, Olga
AU - Melone, Marina A B
AU - De Michele, Giuseppe
AU - Federico, Antonio
AU - Bertini, Enrico
AU - Durr, Alexandra
AU - Brockmann, Knut
AU - Van Der Knaap, Marjo S.
AU - Zatz, Mayana
AU - Filla, Alessandro
AU - Brice, Alexis
AU - Stevanin, Giovanni
AU - Santorelli, Filippo M.
PY - 2009/3
Y1 - 2009/3
N2 - 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.
AB - 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.
KW - ARHSP
KW - Mutation screening
KW - SPG11
KW - TCC
UR - http://www.scopus.com/inward/record.url?scp=61649106518&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=61649106518&partnerID=8YFLogxK
U2 - 10.1002/humu.20945
DO - 10.1002/humu.20945
M3 - Article
C2 - 19105190
AN - SCOPUS:61649106518
VL - 30
JO - Human Mutation
JF - Human Mutation
SN - 1059-7794
IS - 3
ER -