Wolf-Hirschhorn syndrome: A review and update
Wolf-Hirschhorn syndrome: A review and update
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DOI：
10.1002/ajmg.c.31449
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发表时间：
2015-09-01
影响因子：
3.1
通讯作者：
South, Sarah T.
中科院分区：
文献类型：
--
作者：
Battaglia, Agatino;Carey, John C.;South, Sarah T.
自从1961年4P首次被描述以来，我们对这一经典的缺失障碍的理解已经取得了重大进展。我们已经能够建立与远端4p单体相关的WHS表型的更完整的图景，我们正在努力描绘当远端4p上的每个基因是半合子时的表型效应。我们的目标是为诊断为WHS的个体的家庭提供特定于基因的预测性指导和建议。此外，确定这种疾病的分子基础可能会为分子治疗提供靶点。因此，下一步是确定特定基因缺失的确切影响。随着我们期待加深对远端4p缺失的理解，我们的重点将继续放在建立稳健的基因型-表型相关性和这些表型的外显性上。随着年龄的增长，我们将继续密切关注我们的WHS队列，以确定是否存在这些并存疾病，包括肝脏肿瘤、造血功能障碍和癫痫复发。我们还将继续提炼其他表型的关键区域，因为我们招募了更多的(希望提供信息的)参与者加入研究研究，并阐明了这些区域的基因机制。还将开发新的动物模型，以加深我们对半合子影响的理解，并作为治疗开发的模型。(C)2015年威利期刊公司。
Since 4p- was first described in 1961, significant progress has been made in our understanding of this classic deletion disorder. We have been able to establish a more complete picture of the WHS phenotype associated with distal 4p monosomy, and we are working to delineate the phenotypic effects when each gene on distal 4p is hemizygous. Our aim is to provide genotype-specific anticipatory guidance and recommendations to families of individuals with a diagnosis of WHS. In addition, establishing the molecular underpinnings of the disorder will potentially suggest targets for molecular treatments. Thus, the next step is to determine the precise effects of specific gene deletions. As we look forward to deepening our understanding of distal 4p deletion, our focus will continue to be on the establishment of robust genotype-phenotype correlations and the penetrance of these phenotypes. We will continue to follow our WHS cohort closely as they age to determine the presence or absence of some of these comorbidities, including hepatic neoplasms, hematopoietic dysfunction, and recurrence of seizures. We will also continue to refine the critical regions for other phenotypes as we enroll additional (hopefully informative) participants into the research study and as the mechanisms of the genes in these regions are elucidated. New animal models will also be developed to further our understanding of the effects of hemizygosity as well as to serve as models for treatment development. (c) 2015 Wiley Periodicals, Inc.