The etiology of Wolf-Hirschhorn syndrome.
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.
Bergemann
Andrew D
AD
Department of Pathology, The Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA. andrew.bergemann@mssm.edu
Cole
Francesca
F
Hirschhorn
Kurt
K
D000015:Abnormalities, Multiple / Q000235:genetics*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002872:Chromosome Deletion; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000235:genetics; D004195:Disease Models, Animal; D006130:Growth Disorders / Q000235:genetics; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D013577:Syndrome; D016335:Zinc Fingers
D002352:Carrier Proteins; D012097:Repressor Proteins; D011495:Histone-Lysine N-Methyltransferase; C419586:NSD2 protein, human