A periodic tryptophan protein 2 gene homologue (PWP2H) in the candidate region of progressive myoclonus epilepsy on 21q22.3.
The Unverricht-Lundborg type of progressive myoclonus epilepsy (EPM1) has been mapped to human chromosome 21q22.3, and the candidate region has been narrowed to a region of less than 300 kb. We now report the isolation of a novel gene, PWP2H, from this EPM1 candidate region. The putative protein encoded by this gene is a novel member of the beta transducin protein superfamily with high homology to the yeast periodic tryptophan protein 2 (PWP2). PWP2H cDNA was isolated from a 14 week human trisomy 21 fetal brain cDNA library by using a modification of a direct cDNA selection method. PFGE analysis showed that PWP2H is located proximal to D21S25 and distal to TMEM1. Northern analysis of the 3.1-kb PWP2H cDNA revealed that a 3.3-kb major transcript is ubiquitously expressed in human adult tissues. DNA sequence analysis reveals a complete coding region of 2,610 bp as well as 5'- and 3'-UTR. The structure of the putative PWP2H protein contains 6 WD40 repeats, 2 acidic regions and one leucine zipper domain, suggesting that the protein may form specific protein complexes in which the WD40 repeats and the leucine zipper represent protein-protein binding sites. In conclusion, the map location and the homology to a gene family involved in a large variety of biological processes including signal transduction and development make PWP2H an intriguing candidate for EPM1 as well as for APECED (autoimmune polyglandular disease) and HPE1 (holoprosencephaly-1) that also map in this region of chromosome 21.
Ahmanson Department of Pediatrics, Cedars-Sinai Research Institute, UCLA, USA.
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Yamakawa
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Gao
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Korenberg
D000595:Amino Acid Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002891:Chromosomes, Human, Pair 21; D018076:DNA, Complementary / Q000302:isolation & purification; D004314:Down Syndrome; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D005333:Fetus; D006801:Humans; D015151:Immunoblotting; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics*; D015183:Restriction Mapping; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D017422:Sequence Analysis, DNA; D015003:Yeasts / Q000235:genetics
D018076:DNA, Complementary; C100850:PWP2 protein, S cerevisiae; C484410:PWP2 protein, human; D011506:Proteins; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins