title: LIS1-related isolated lissencephaly: spectrum of mutations and relationships with malformation severity.
abstract: 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.
  
  
  METHODS
  Retrospective study. Subjects A total of 63 patients with posteriorly predominant lissencephaly.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: 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, France.
authors: Yoann
authors: Y
authors: Saillour
authors: Nathalie
authors: N
authors: Carion
authors: Chloé
authors: C
authors: Quelin
authors: Pierre-Louis
authors: PL
authors: Leger
authors: Nathalie
authors: N
authors: Boddaert
authors: Caroline
authors: C
authors: Elie
authors: Annick
authors: A
authors: Toutain
authors: Sandra
authors: S
authors: Mercier
authors: Marie Anne
authors: MA
authors: Barthez
authors: Mathieu
authors: M
authors: Milh
authors: Sylvie
authors: S
authors: Joriot
authors: Vincent
authors: V
authors: des Portes
authors: Nicole
authors: N
authors: Philip
authors: Dominique
authors: D
authors: Broglin
authors: Agathe
authors: A
authors: Roubertie
authors: Gaelle
authors: G
authors: Pitelet
authors: Marie Laure
authors: ML
authors: Moutard
authors: Jean Marc
authors: JM
authors: Pinard
authors: Claude
authors: C
authors: Cances
authors: Anna
authors: A
authors: Kaminska
authors: Jamel
authors: J
authors: Chelly
authors: Chérif
authors: C
authors: Beldjord
authors: Nadia
authors: N
authors: Bahi-Buisson
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D054221:Classical Lissencephalies and Subcortical Band Heterotopias / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009460:Neurologic Examination; D010641:Phenotype; D055815:Young Adult
chemical_list: D008869:Microtubule-Associated Proteins; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human