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

作者：Komoike Yuta; Shimojima Keiko; Liang Jao Shwann; Fujii Hiroshi; Maegaki Yoshihiro; Osawa Makiko; Fujii Sakiko; Higashinakagawa Toru; Yamamoto Toshiyuki^*

来源：Journal of Human Genetics, 2010, 55(3): 155-162.

DOI：10.1038/jhg.2010.1

• array-based comparative genomic hybridization (array-CGH)
• DLG4/PSD95
• GABARAP
• GPS2
• KCTD11
• microdeletion
• neurodevelopment
• 17p13.1

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. Journal of Human Genetics (2010) 55, 155-162; doi: 10.1038/jhg.2010.1; published online 29 January 2010

• 出版日期2010-3