Document Detail

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.
MedLine Citation:
PMID:  9618163     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Human molecular genetics     Volume:  7     ISSN:  0964-6906     ISO Abbreviation:  Hum. Mol. Genet.     Publication Date:  1998 Jul 
Date Detail:
Created Date:  1999-01-12     Completed Date:  1999-01-12     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1071-82     Citation Subset:  IM    
MGC-Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/AF083386;  AF083387;  AF083388;  AF083389;  AF083390;  AF083391
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MeSH Terms
Amino Acid Sequence
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
Immunoglobulin Heavy Chains / genetics*
Molecular Sequence Data
Multiple Myeloma / genetics*
Protein Biosynthesis
Proteins / genetics*
Sequence Homology, Amino Acid
Sequence Homology, Nucleic Acid
Transcription Factors
Translocation, Genetic*
Reg. No./Substance:
0/Chromosomal Proteins, Non-Histone; 0/Histone Chaperones; 0/Immunoglobulin Heavy Chains; 0/Proteins; 0/SET protein, human; 0/Transcription Factors
Erratum In:
Hum Mol Genet 1998 Sep;7(9):1527

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