Document Detail


Human lissencephaly with cerebellar hypoplasia due to mutations in TUBA1A: expansion of the foetal neuropathological phenotype.
MedLine Citation:
PMID:  20376468     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Neuronal migration disorders account for a substantial number of cortical malformations, the most severe forms being represented by lissencephalies. Classical lissencephaly has been shown to result from mutations in LIS1 (PAFAH1B1; MIM#601545), DCX (Doublecortin; MIM#300121), ARX (Aristaless-related homeobox gene; MIM#300382), RELN (Reelin; MIM#600514) and VLDLR (Very low density lipoprotein receptor; MIM#224050). More recently, de novo missense mutations in the alpha-tubulin 1a gene (TUBA1A) located on chromosome 12q13.12, have also been associated with more or less severe defects of cortical development, resulting in complete agyria in the most severe cases of lissencephaly. We report here the cerebral lesions in a 36 weeks' gestation female foetus with a novel de novo missense mutation in the TUBA1A gene, presenting the most severe antenatal phenotype reported so far. Using routine immunohistochemistry and confocal microscopy, we show evidence for defects in axonal transport in addition to defects in neuronal migration and differentiation, giving new insights to the pathophysiology of this form of lissencephaly.
Authors:
Magalie Lecourtois; Karine Poirier; Gaëlle Friocourt; Xavier Jaglin; Alice Goldenberg; Pascale Saugier-Veber; Jamel Chelly; Annie Laquerrière
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Publication Detail:
Type:  Case Reports; Journal Article     Date:  2010-04-08
Journal Detail:
Title:  Acta neuropathologica     Volume:  119     ISSN:  1432-0533     ISO Abbreviation:  Acta Neuropathol.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-07     Completed Date:  2010-08-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0412041     Medline TA:  Acta Neuropathol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  779-89     Citation Subset:  IM    
Affiliation:
Faculty of Medicine, INSERM, U614, IFRMP23, Rouen Institute for Medical Research and Innovation, University of Rouen, Rouen, France.
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MeSH Terms
Descriptor/Qualifier:
Axonal Transport
Brain / embryology,  pathology
Cell Differentiation
Cell Movement
Cerebellar Diseases / genetics*,  pathology*
Fatal Outcome
Female
Fetus / pathology
Humans
Immunohistochemistry
Lissencephaly / genetics*,  pathology*
Microscopy, Confocal
Models, Molecular
Mutation, Missense*
Neurogenesis
Neurons / pathology
Phenotype
Protein Structure, Secondary
Tubulin / chemistry,  genetics*
Chemical
Reg. No./Substance:
0/TUBA1A protein, human; 0/Tubulin

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