| WHSC1, a 90 kb SET domain-containing gene, expressed in early development and homologous to a Drosophila dysmorphy gene maps in the Wolf-Hirschhorn syndrome critical region and is fused to IgH in t(4;14) multiple myeloma. | |
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MedLine Citation:
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PMID: 9618163 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Wolf-Hirschhorn syndrome (WHS) is a malformation syndrome associated with a hemizygous deletion of the distal short arm of chromosome 4 (4p16.3). The smallest region of overlap between WHS patients, the WHS critical region, has been confined to 165 kb, of which the complete sequence is known. We have identified and studied a 90 kb gene, designated as WHSC1 , mapping to the 165 kb WHS critical region. This 25 exon gene is expressed ubiquitously in early development and undergoes complex alternative splicing and differential polyadenylation. It encodes a 136 kDa protein containing four domains present in other developmental proteins: a PWWP domain, an HMG box, a SET domain also found in the Drosophila dysmorphy gene ash -encoded protein, and a PHD-type zinc finger. It is expressed preferentially in rapidly growing embryonic tissues, in a pattern corresponding to affected organs in WHS patients. The nature of the protein motifs, the expression pattern and its mapping to the critical region led us to propose WHSC1 as a good candidate gene to be responsible for many of the phenotypic features of WHS. Finally, as a serendipitous finding, of the t(4;14) (p16.3;q32.3) translocations recently described in multiple myelomas, at least three breakpoints merge the IgH and WHSC1 genes, potentially causing fusion proteins replacing WHSC1 exons 1-4 by the IgH 5'-VDJ moiety. |
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Authors:
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I Stec; T J Wright; G J van Ommen; P A de Boer; A van Haeringen; A F Moorman; M R Altherr; J T den Dunnen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Human molecular genetics Volume: 7 ISSN: 0964-6906 ISO Abbreviation: Hum. Mol. Genet. Publication Date: 1998 Jul |
Date Detail:
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Created Date: 1999-01-12 Completed Date: 1999-01-12 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9208958 Medline TA: Hum Mol Genet Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 1071-82 Citation Subset: IM |
Affiliation:
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MGC-Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GENBANK/AF083386; AF083387; AF083388; AF083389; AF083390; AF083391 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Base Composition Blotting, Northern Chromosomal Proteins, Non-Histone Chromosomes, Human, Pair 14 / genetics* Chromosomes, Human, Pair 4 / genetics* Gene Expression Regulation, Developmental* Genes, Immunoglobulin Genes, Neoplasm Histone Chaperones Humans Immunoglobulin Heavy Chains / genetics* Male Mice Molecular Sequence Data Multiple Myeloma / genetics* Protein Biosynthesis Proteins / genetics* Sequence Homology, Amino Acid Sequence Homology, Nucleic Acid Syndrome Transcription Factors Translocation, Genetic* |
| Chemical | |
Reg. No./Substance:
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0/Chromosomal Proteins, Non-Histone; 0/Histone Chaperones; 0/Immunoglobulin Heavy Chains; 0/Proteins; 0/SET protein, human; 0/Transcription Factors |
| Comments/Corrections | |
Erratum In:
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Hum Mol Genet 1998 Sep;7(9):1527 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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