Human Molecular Genetics Advance Access published online on April 20, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi157
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Human Genetics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA
* To whom correspondence should be addressed. Hydrolethalus syndrome (HLS) is an autosomal recessive lethal malformation syndrome characterized by multiple developmental defects of fetus. We have earlier mapped and restricted the HLS region to a critical 1 cM interval on 11q23-25. The LD and haplotype analysis of single nucleotide polymorphism (SNP) markers helped to further restrict the HLS locus to 476 kb between genes PKNOX2 and DDX25. An HLS associated mutation was identified in a novel regional transcript (GenBank accession number FLJ32915), referred here to as the HYLS1 gene. The identified A to G transition results in a D211G change in the predicted 299 amino acid polypeptide with unknown function. The HYLS1 gene shows alternative splicing and the transcript is found in multiple tissues during fetal development. In situ hybridization shows spatial and temporal distribution of transcripts well in agreement with the tissue phenotype of HLS patients Immunostaining of in vitro expressed polypeptides from wild-type (WT) cDNA revealed cytoplasmic staining whereas mutant polypeptides became localized in distinct nuclear structures, implying a disturbed cellular localization of the mutant protein. The Drosophila melanogaster model confirmed these findings and provide evidence for the significance of the mutation both in vitro and in vivo.
Received January 14, 2005
Revised March 11, 2005
Accepted April 8, 2005
Article
Hydrolethalus syndrome is caused by a missense mutation in a novel gene HYLS1
2 Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland
3 Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland; Neuroscience Center, University of Helsinki, Helsinki, Finland
4 Department of Human Genetics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA; Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland
5 Neurogenetics Program, Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA
6 Neurogenetics Program, Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA; Brain Research Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA; Center for Neurobehavioral Genetics, Neuropsychiatric Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
7 Department of Medical Genetics, Family Federation of Finland, Helsinki, Finland
8 Department of Human Genetics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA; Department of Molecular Medicine, National Public Health Institute, Biomedicum Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland
Leena Peltonen, E-mail: leena.peltonen{at}ktl.fi
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Dammermann, H. Pemble, B. J. Mitchell, I. McLeod, J. R. Yates III, C. Kintner, A. B. Desai, and K. Oegema The hydrolethalus syndrome protein HYLS-1 links core centriole structure to cilia formation Genes & Dev., September 1, 2009; 23(17): 2046 - 2059. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Zhang, M.-J. Yi, X. Chen, F. Cole, R. S. Krauss, and J.-S. Kang Cortical Thinning and Hydrocephalus in Mice Lacking the Immunoglobulin Superfamily Member CDO Mol. Cell. Biol., May 15, 2006; 26(10): 3764 - 3772. [Abstract] [Full Text] [PDF]
|
|