TY - JOUR
T1 - The etiology of Wolf-Hirschhorn syndrome
AU - Bergemann, Andrew D.
AU - Cole, Francesca
AU - Hirschhorn, Kurt
N1 - Funding Information:
We thank the researchers in the WHS field for their remarkable contributions to the understanding of the pathogenesis of this disorder. We also thank Robert S. Krauss for his support and assistance. This work was completed with funding from the NICHD (HD36871) and from the Gaisman Frontiers of Biomedical Sciences Research Award.
PY - 2005/3
Y1 - 2005/3
N2 - Wolf-Hirschhorn syndrome (WHS) is defined by a collection of core characteristics, which include mental retardation, epilepsy, growth delay and cranio-facial dysgenesis. The disorder is caused by sub-telomeric deletions in the short arm of chromosome 4. The severity of the core characteristics is highly variable, and additional problems, including midline fusion defects, occur at lower frequency. Only one gene, WHSC1, is deleted in every case. However, recent evidence, from patient studies and mouse models, indicates that deletion of WHSC1 alone is insufficient for full-blown WHS. Instead a model is emerging in which deletion of WHSC1 is essential for pathogenesis, but deletion of linked genes contributes to both the severity of the core characteristics and the presence of the additional syndromic problems. In this article, we outline the progress being made in patient studies and in the development of mouse models, and relate the implications of this work for a broad group of sub-telomeric deletion syndromes.
AB - Wolf-Hirschhorn syndrome (WHS) is defined by a collection of core characteristics, which include mental retardation, epilepsy, growth delay and cranio-facial dysgenesis. The disorder is caused by sub-telomeric deletions in the short arm of chromosome 4. The severity of the core characteristics is highly variable, and additional problems, including midline fusion defects, occur at lower frequency. Only one gene, WHSC1, is deleted in every case. However, recent evidence, from patient studies and mouse models, indicates that deletion of WHSC1 alone is insufficient for full-blown WHS. Instead a model is emerging in which deletion of WHSC1 is essential for pathogenesis, but deletion of linked genes contributes to both the severity of the core characteristics and the presence of the additional syndromic problems. In this article, we outline the progress being made in patient studies and in the development of mouse models, and relate the implications of this work for a broad group of sub-telomeric deletion syndromes.
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U2 - 10.1016/j.tig.2005.01.008
DO - 10.1016/j.tig.2005.01.008
M3 - Review article
C2 - 15734578
AN - SCOPUS:13944273804
SN - 0168-9525
VL - 21
SP - 188
EP - 195
JO - Trends in Genetics
JF - Trends in Genetics
IS - 3
ER -