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Screening of ARHSP‐TCC patients expands the spectrum of SPG11 mutations and includes a large scale gene deletion
Author(s) -
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,
Di Rocco Maja,
Bueno Clarissa,
Malandrini Alessandro,
Battini Roberta,
Sickl Elisabeth,
de Leva Maria Fulvia,
BoespflugTanguy 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.,
De Michele Giuseppe,
Federico Antonio,
Bertini Enrico,
Durr Alexandra,
Brockmann Knut,
van der Knaap Marjo S.,
Zatz Mayana,
Filla Alessandro,
Brice Alexis,
Stevanin Giovanni,
Santorelli Filippo M.
Publication year - 2009
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20945
Subject(s) - biology , genetics , missense mutation , multiplex ligation dependent probe amplification , hereditary spastic paraplegia , nonsense mutation , population , mutation , gene , gene duplication , exon , phenotype , medicine , environmental health
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.