PUBLICATION

A functional analysis of GABARAP on 17p13.1 by knockdown zebrafish

Authors
Komoike, Y., Shimojima, K., Liang, J.S., Fujii, H., Maegaki, Y., Osawa, M., Fujii, S., Higashinakagawa, T., and Yamamoto, T.
ID
ZDB-PUB-100202-14
Date
2010
Source
Journal of Human Genetics   55(3): 155-162 (Journal)
Registered Authors
Keywords
array-based comparative genomic hybridization (array-CGH), DLG4/PSD95, GABARAP, GPS2, KCTD11, microdeletion, neurodevelopment, 17p13.1
MeSH Terms
  • Adaptor Proteins, Signal Transducing/genetics
  • Adaptor Proteins, Signal Transducing/metabolism*
  • Adult
  • Animals
  • Brain/drug effects
  • Brain/growth & development
  • Brain/pathology
  • Carrier Proteins/genetics
  • Carrier Proteins/metabolism*
  • Child
  • Chromosome Deletion
  • Chromosomes, Human, Pair 17/genetics*
  • Cytogenetic Analysis
  • DNA Mutational Analysis
  • Female
  • Gene Knockdown Techniques*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism
  • Microtubule-Associated Proteins/genetics
  • Microtubule-Associated Proteins/metabolism*
  • Oligonucleotides, Antisense/pharmacology
  • Pregnancy
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
20111057 Full text @ J. Hum. Genet.
Abstract
Array-based comparative genomic hybridization identified a 2.3-Mb microdeletion of 17p13.2p13.1 in a boy presenting with moderate mental retardation, intractable epilepsy and dysmorphic features. This deletion region was overlapped with the previously proposed shortest region overlapped for microdeletion of 17p13.1 in patients with mental retardation, microcephaly, microretrognathia and abnormal magnetic resonance imaging (MRI) findings of cerebral white matter, in which at least 17 known genes are included. Among them, DLG4/PSD95, GPS2, GABARAP and KCTD11 have a function in neuronal development. Because of the functional importance, we paid attention to DLG4/PSD95 and GABARAP, and analyzed zebrafish in which the zebrafish homolog of human DLG4/PSD95 and GABARAP was knocked down and found that gabarap knockdown resulted in small head and hypoplastic mandible. This finding would be similar to the common findings of the patients with 17p13.1 deletions. Although there were no pathogenic mutations in DLG4/PSD95 or GABARAP in a cohort study with 142 patients with idiopathic developmental delay with/without epilepsy, further studies would be required for genes included in this region.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping