Micro-réarrangements chromosomiques et déficience intellectuelle : identification de nouveaux gènes et caractérisation des conséquences moléculaires de ces micro-réarrangements sur les gènes cibles

Abstract : A lot of intellectual disability (ID) genes have to be discovered. One of the approaches to identify new ID genes is to characterize chromosomal aberrations in affected patients. Array-CGH (Comparative Genomic Hybridization) made it possible to detect small CNV (Copy Number Variations) affecting only one or a few genes. Molecular outcomes of these microdeletions and microduplications are different depending on the position of the gene relative to the breakpoints. We have thus shown the involvement of MBD5 gene in the 2q23.1 microdeletion syndrome and in ID with the characterization of three partial deletions, a partial duplication and the first nonsense mutation described in this gene. We have also described in patients with severe ID a new syndrome associated with 4q21 deletions involving two candidate genes: PRKG2 and RASGEF1B. This syndrome is associated with a recognizable clinical phenotype with marked growth restriction, severe psychomotor delay and absent or severely delayed speech. In addition, we have studied two Xq24q25 duplications affecting GRIA3 gene in boys with ID. The first one affects partially the gene, the second one is located upstream of the gene and is responsible for a position effect. Finally we have studied a consanguineous family with a 8p22 duplication affecting partially TUSC3 gene which is involved in autosomal recessive ID
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http://docnum.univ-lorraine.fr/prive/DDOC_T_2012_0308_BONNET.pdf
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Submitted on : Thursday, March 29, 2018 - 12:22:23 PM
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Céline Bonnet. Micro-réarrangements chromosomiques et déficience intellectuelle : identification de nouveaux gènes et caractérisation des conséquences moléculaires de ces micro-réarrangements sur les gènes cibles. Médecine humaine et pathologie. Université de Lorraine, 2012. Français. ⟨NNT : 2012LORR0308⟩. ⟨tel-01749653⟩

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