Human Molecular Genetics Advance Access originally published online on April 20, 2005
Human Molecular Genetics 2005 14(11):1475-1488; doi:10.1093/hmg/ddi157
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hydrolethalus syndrome is caused by a missense mutation in a novel gene HYLS1
1Department of Human Genetics, 2Neurogenetics Program, Department of Neurology, 3Brain Research Institute and 4Center for Neurobehavioral Genetics, Neuropsychiatric Institute, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA, 5Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland, 6Neuroscience Center, University of Helsinki, Helsinki, Finland, 7Department of Medical Genetics, Family Federation of Finland, Helsinki, Finland and 8Department of Medical Genetics, University of Helsinki, Helsinki, Finland
* To whom correspondence should be addressed at: Biomedicum Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland. Tel: +358 947448393; Fax: +358 947448480; Email: leena.peltonen{at}ktl.fi
Received January 14, 2005; Revised March 11, 2005; Accepted April 8, 2005
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 linkage disequilibrium (LD) and haplotype analyses 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 no. FLJ32915), referred to here as the HYLS1 gene. The identified A to G transition results in a D211G change in the 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 distributions of transcripts in good 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 provides evidence for the significance of the mutation both in vitro and in vivo.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
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]
|
|