Screening of ARHSP-TCC patients expands the spectrum of SPG11 mutations and includes a large scale gene deletion.
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.
Denora
Paola S
PS
INSERM, UMR_S679, Paris, France .
Schlesinger
David
D
Casali
Carlo
C
Kok
Fernando
F
Tessa
Alessandra
A
Boukhris
Amir
A
Azzedine
Hamid
H
Dotti
Maria Teresa
MT
Bruno
Claudio
C
Truchetto
Jeremy
J
Biancheri
Roberta
R
Fedirko
Estelle
E
Di Rocco
Maja
M
Bueno
Clarissa
C
Malandrini
Alessandro
A
Battini
Roberta
R
Sickl
Elisabeth
E
de Leva
Maria Fulvia
MF
Boespflug-Tanguy
Odile
O
Silvestri
Gabriella
G
Simonati
Alessandro
A
Said
Edith
E
Ferbert
Andreas
A
Criscuolo
Chiara
C
Heinimann
Karl
K
Modoni
Anna
A
Weber
Peter
P
Palmeri
Silvia
S
Plasilova
Martina
M
Pauri
Flavia
F
Cassandrini
Denise
D
Battisti
Carla
C
Pini
Antonella
A
Tosetti
Michela
M
Hauser
Erwin
E
Masciullo
Marcella
M
Di Fabio
Roberto
R
Piccolo
Francesca
F
Denis
Elodie
E
Cioni
Giovanni
G
Massa
Roberto
R
Della Giustina
Elvio
E
Calabrese
Olga
O
Melone
Marina A B
MA
De Michele
Giuseppe
G
Federico
Antonio
A
Bertini
Enrico
E
Durr
Alexandra
A
Brockmann
Knut
K
van der Knaap
Marjo S
MS
Zatz
Mayana
M
Filla
Alessandro
A
Brice
Alexis
A
Stevanin
Giovanni
G
Santorelli
Filippo M
FM
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
D011506:Proteins; C520412:SPG11 protein, human