This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in this journal  Topic Collections  • Epilepsy  • Neurogenetics  • Pediatric Neurology  • Neurology, Other  • Genetics, Other  • Alert me on articles by topic  Social Bookmarking   What's this?

Spectrum of Mutations and Relationships With Malformation Severity

Yoann Saillour, PhD; Nathalie Carion, MS; Chloé Quelin, MD; Pierre-Louis Leger, MD; Nathalie Boddaert, MD, PhD; Caroline Elie, MD; Annick Toutain, MD, PhD; Sandra Mercier, MD; Marie Anne Barthez, MD; Mathieu Milh, MD, PhD; Sylvie Joriot, MD; Vincent des Portes, MD, PhD; Nicole Philip, MD, PhD; Dominique Broglin, MD; Agathe Roubertie, MD, PhD; Gaelle Pitelet, MD; Marie Laure Moutard, MD; Jean Marc Pinard, MD; Claude Cances, MD; Anna Kaminska, MD; Jamel Chelly, MD, PhD; Chérif Beldjord, MD, PhD; Nadia Bahi-Buisson, MD, PhD

Arch Neurol. 2009;66(8):1007-1015.

Objective  With the largest data set of patients with LIS1-related lissencephaly, the major cause of posteriorly predominant lissencephaly related to either LIS1 mutation or intragenic deletion, described so far, we aimed to refine the spectrum of neurological and radiological features and to assess relationships with the genotype.

Design  Retrospective study.

Subjects  A total of 63 patients with posteriorly predominant lissencephaly.

Interventions  Of the 63 patients, 40 were found to carry either LIS1 point mutations (77.5%) or small genomic deletions (20%), and 1 carried a somatic nonsense mutation. On the basis of the severity of neuromotor impairment, epilepsy, and radiological findings, correlations with the location and type of mutation were examined.

Results  Most patients with LIS1 mutations demonstrated posterior agyria (grade 3a, 55.3%) with thin corpus callosum (50%) and prominent perivascular spaces (67.4%). By contrast, patients without LIS1 mutations tended to have less severe lissencephaly (grade 4a, 41.6%) and no additional brain abnormalities. The degree of neuromotor impairment was in accordance with the severity of lissencephaly, with a high incidence of tetraplegia (61.1%). Conversely, the severity of epilepsy was not determined with the same reliability because 82.9% had early onset of seizures and 48.7% had seizures more often than daily. In addition, neither the mutation type nor the location of the mutation were found to predict the severity of LIS1-related lissencephaly.

Conclusion  Our results confirm the homogeneity profile of patients with LIS1-related lissencephaly who demonstrate in a large proportion Dobyns lissencephaly grade 3a, and the absence of correlation with LIS1 mutations.

Author Affiliations: Conseil National de la Recherche Scientifique, Université Paris Descartes (Unités Mixtes de Recherche 8104) and Institut national de la santé et de la recherche médicale (INSERM) U567, Paris (Drs Saillour, Quelin, Chelly, Beldjord, and Bahi-Buisson), Institut Cochin, Paris; Laboratoire de Génétique Moléculaire, Pavillon Cassini, Hopital Cochin, Assistance publique Hopitaux de Paris (AP-HP), Université Paris Descartes, Paris (Drs Carion, Chelly, and Beldjord); Service de Neurologie Pédiatrique, Département de Pédiatrie (Drs Leger and Bahi-Buisson), Service de Radiologie Pédiatrique (Dr Boddaert), Unité de bioinformatique (Dr Elie), and Laboratoire de Neurophysiologie (Dr Kaminska), Hospital Necker Enfants Malades, AP-HP, Université Paris Descartes, Paris; INSERM U797–Commissariat à l’Energie Atomique (CEA), Orsay (Dr Boddaert); Service de Génétique (Drs Toutain and Mercier) and Service de Neuropédiatrie (Dr Barthez), Hopital Clocheville, Centre Hospitalo-Universitaire (CHU) de Tours, Tours; Assistance publique Hopitaux de Marseille Neurologie Pediatrique, Marseille (Dr Milh); Service de Neuropédiatrie, Clinique Hopital, Jeanne de Flandres Centre Hospitalo-Universitaire de Lille, Lille (Dr Joriot); Service de Neuropédiatrie, CHU Lyon, Lyon (Dr des Portes); Service de Genetique, Hopital La Timone, CHU Marseille, Marseille (Dr Philip); Service de Neurologie, Centre Saint Paul, Marseille (Dr Broglin); Service de Neuropédiatrie, CHU Montpellier, Montpellier (Dr Roubertie); Service de Neuropédiatrie, CHU Nice, Nice (Dr Pitelet); Service de Neurologie Pédiatrique, Hopital Trousseau, AP-HP, Paris (Dr Moutard); Service de Neurologie Pédiatrique, Hopital Raymond Poincaré Garches, AP-HP, Université Paris Descartes, Paris (Dr Pinard); Service de Neurologie Pédiatrique, Hopital des Enfants, CHU Toulouse, Toulouse (Dr Cances); and INSERM U663, Paris, France (Drs Kaminska and Bahi-Buisson).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED ARTICLE

This Month in Archives of Neurology
Arch Neurol. 2009;66(8):929-930.
FULL TEXT