title: Screening of ARHSP-TCC patients expands the spectrum of SPG11 mutations and includes a large scale gene deletion.
abstract: 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.
authors.affiliation: INSERM, UMR_S679, Paris, France .
authors.forename: Paola S
authors.initials: PS
authors.lastname: Denora
authors.forename: David
authors.initials: D
authors.lastname: Schlesinger
authors.forename: Carlo
authors.initials: C
authors.lastname: Casali
authors.forename: Fernando
authors.initials: F
authors.lastname: Kok
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tessa
authors.forename: Amir
authors.initials: A
authors.lastname: Boukhris
authors.forename: Hamid
authors.initials: H
authors.lastname: Azzedine
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Dotti
authors.forename: Claudio
authors.initials: C
authors.lastname: Bruno
authors.forename: Jeremy
authors.initials: J
authors.lastname: Truchetto
authors.forename: Roberta
authors.initials: R
authors.lastname: Biancheri
authors.forename: Estelle
authors.initials: E
authors.lastname: Fedirko
authors.forename: Maja
authors.initials: M
authors.lastname: Di Rocco
authors.forename: Clarissa
authors.initials: C
authors.lastname: Bueno
authors.forename: Alessandro
authors.initials: A
authors.lastname: Malandrini
authors.forename: Roberta
authors.initials: R
authors.lastname: Battini
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Sickl
authors.forename: Maria Fulvia
authors.initials: MF
authors.lastname: de Leva
authors.forename: Odile
authors.initials: O
authors.lastname: Boespflug-Tanguy
authors.forename: Gabriella
authors.initials: G
authors.lastname: Silvestri
authors.forename: Alessandro
authors.initials: A
authors.lastname: Simonati
authors.forename: Edith
authors.initials: E
authors.lastname: Said
authors.forename: Andreas
authors.initials: A
authors.lastname: Ferbert
authors.forename: Chiara
authors.initials: C
authors.lastname: Criscuolo
authors.forename: Karl
authors.initials: K
authors.lastname: Heinimann
authors.forename: Anna
authors.initials: A
authors.lastname: Modoni
authors.forename: Peter
authors.initials: P
authors.lastname: Weber
authors.forename: Silvia
authors.initials: S
authors.lastname: Palmeri
authors.forename: Martina
authors.initials: M
authors.lastname: Plasilova
authors.forename: Flavia
authors.initials: F
authors.lastname: Pauri
authors.forename: Denise
authors.initials: D
authors.lastname: Cassandrini
authors.forename: Carla
authors.initials: C
authors.lastname: Battisti
authors.forename: Antonella
authors.initials: A
authors.lastname: Pini
authors.forename: Michela
authors.initials: M
authors.lastname: Tosetti
authors.forename: Erwin
authors.initials: E
authors.lastname: Hauser
authors.forename: Marcella
authors.initials: M
authors.lastname: Masciullo
authors.forename: Roberto
authors.initials: R
authors.lastname: Di Fabio
authors.forename: Francesca
authors.initials: F
authors.lastname: Piccolo
authors.forename: Elodie
authors.initials: E
authors.lastname: Denis
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cioni
authors.forename: Roberto
authors.initials: R
authors.lastname: Massa
authors.forename: Elvio
authors.initials: E
authors.lastname: Della Giustina
authors.forename: Olga
authors.initials: O
authors.lastname: Calabrese
authors.forename: Marina A B
authors.initials: MA
authors.lastname: Melone
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Michele
authors.forename: Antonio
authors.initials: A
authors.lastname: Federico
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.forename: Knut
authors.initials: K
authors.lastname: Brockmann
authors.forename: Marjo S
authors.initials: MS
authors.lastname: van der Knaap
authors.forename: Mayana
authors.initials: M
authors.lastname: Zatz
authors.forename: Alessandro
authors.initials: A
authors.lastname: Filla
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stevanin
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Santorelli
mesh_terms: D000293:Adolescent; D000328:Adult; D061085:Agenesis of Corpus Callosum; D000462:Algeria; D001483:Base Sequence; D001938:Brazil; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D005808:Genes, Recessive; D005820:Genetic Testing; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009018:Morocco; D009154:Mutation; D010375:Pedigree; D011174:Portugal; D011506:Proteins / Q000235:genetics*; D015419:Spastic Paraplegia, Hereditary / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D055815:Young Adult
chemical_list: D011506:Proteins; C520412:SPG11 protein, human