Artículos de revistas
Screening of ARHSP-TCC Patients Expands the Spectrum of SPG11 Mutations and Includes a Large Scale Gene Deletion
Fecha
2009Registro en:
HUMAN MUTATION, v.30, n.3, p.E500-E519, 2009
1059-7794
10.1002/humu.20945
Autor
DENORA, Paola S.
SCHLESINGER, David
CASALI, Carlo
KOK, Fernando
TESSA, Alessandra
BOUKHRIS, Amir
AZZEDINE, Hamid
DOTTI, Maria Teresa
BRUNO, Claudio
TRUCHETTO, Jeremy
BIANCHERI, Roberta
FEDIRKO, Estelle
ROCCO, Maja Di
BUENO, Clarissa
MALANDRINI, Alessandro
BATTINI, Roberta
SICKL, Elisabeth
LEVA, Maria Fulvia de
BOESPFLUG-TANGUY, Odile
SILVESTRI, Gabriella
SIMONATI, Alessandro
SAID, Edith
FERBERT, Andreas
CRISCUOLO, Chiara
HEINIMANN, Karl
MODONI, Anna
WEBER, Peter
PALMERI, Silvia
PLASILOVA, Martina
PAURI, Flavia
CASSANDRINI, Denise
BATTISTI, Carla
PINI, Antonella
TOSETTI, Michela
HAUSER, Erwin
MASCIULLO, Marcella
FABIO, Roberto Di
PICCOLO, Francesca
DENIS, Elodie
CIONI, Giovanni
MASSA, Roberto
GIUSTINA, Elvio Della
CALABRESE, Olga
MELONE, Marina A. B.
MICHELE, Giuseppe De
FEDERICO, Antonio
BERTINI, Enrico
DURR, Alexandra
BROCKMANN, Knut
KNAAP, Marjo S. van der
ZATZ, Mayana
FILLA, Alessandro
BRICE, Alexis
STEVANIN, Giovanni
SANTORELLI, Filippo M.
Institución
Resumen
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. (C) 2008 Wiley-Liss, Inc.