LIS1-related isolated lissencephaly: spectrum of mutations and relationships with malformation severity.

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  • Additional Information
    • Source:
      Publisher: American Medical Assn Country of Publication: United States NLM ID: 0372436 Publication Model: Print Cited Medium: Internet ISSN: 1538-3687 (Electronic) Linking ISSN: 00039942 NLM ISO Abbreviation: Arch Neurol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Chicago, American Medical Assn.
    • Subject Terms:
      DNA Mutational Analysis* ; Genotype* ; Magnetic Resonance Imaging* ; Neurologic Examination*; 1-Alkyl-2-acetylglycerophosphocholine Esterase/*genetics ; Brain/*pathology ; Classical Lissencephalies and Subcortical Band Heterotopias/*genetics ; Microtubule-Associated Proteins/*genetics; Adolescent ; Adult ; Child ; Child, Preschool ; Classical Lissencephalies and Subcortical Band Heterotopias/classification ; Classical Lissencephalies and Subcortical Band Heterotopias/diagnosis ; Female ; Humans ; Infant ; Male ; Phenotype ; Young Adult
    • 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.
      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.
    • Accession Number:
      0 (Microtubule-Associated Proteins)
      EC 3.1.1.47 (1-Alkyl-2-acetylglycerophosphocholine Esterase)
      EC 3.1.1.47 (PAFAH1B1 protein, human)
    • Publication Date:
      Date Created: 20090812 Date Completed: 20090820 Latest Revision: 20090811
    • Publication Date:
      20231215
    • Accession Number:
      10.1001/archneurol.2009.149
    • Accession Number:
      19667223