Disruption of chromodomain helicase DNA binding protein 2 (CHD2) causes scoliosis
Disruption of chromodomain helicase DNA binding protein 2 (CHD2) causes scoliosis
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DOI：
10.1002/ajmg.a.32178
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发表时间：
2008-05-01
影响因子：
2
通讯作者：
Quade, Bradley J.
中科院分区：
文献类型：
--
作者：
Kulkarni, Shashikant;Nagarajan, Prabakaran;Quade, Bradley J.
在此，我们描述了一个明显平衡的从头易位，t（X;15）（p22.2;q26.1）dn，在女性患者脊柱侧凸，多毛，学习问题，发育迟缓（DGAP 025）。其他临床表现包括高弓腭，2-3趾并趾，血清睾酮轻度升高。没有已知或预测的基因被Xp22.2断裂点破坏。15q26.1断裂点破坏染色体结构域解旋酶DNA结合蛋白2（chromodomain helicase DNA binding protein 2，CHD 2）。染色质重塑基因家族的另一个成员CHD 7与一系列先天性异常相关，这些先天性异常包括缺损、心脏异常、后鼻孔闭锁、智力低下、生殖器和耳部异常综合征（CHARGE）和特发性脊柱侧凸。15 q26的单体性也与一系列先天性异常和生长迟缓相关，这些先天性异常和生长迟缓与DGAP 025的先天性异常和生长迟缓重叠。为了提供生物学相关性，我们表征了与胚胎和围产期致死性相关的Chd 2破坏的突变小鼠模型。表达分析表明，Chd 2在胚胎发育的特定时期在心脏、前脑、四肢、面部和背部区域表达。CM 2（+/m）小鼠表现出明显的脊柱后凸、体脂减少、出生后矮小和生长迟缓。这些数据表明，CHD 2的单倍不足可能导致复杂的异常人类表型，包括脊柱侧凸和可能的特征类似于CHARGE综合征。(C)2008 Wiley-Liss，Inc.
Herein we characterize an apparently balanced de novo translocation, t(X;15)(p22.2;q26.1)dn, in a female patient with scoliosis, hirsutisin, learning problems, and developmental delay (DGAP025). Other clinical findings include a high-arched palate, 2-3 syndactyly of the toes, and mildly elevated serum testosterone. No known or predicted genes are disrupted by the Xp22.2 breakpoint. The 15q26.1 breakpoint disrupts chromodomain helicase DNA binding protein 2 (CHD2). Another member of the chromatin-remodeling gene family, CHD7, has been associated with a defined constellation of congenital anomalies known as coloboma, heart anomaly, choanal atresia, mental retardation, genital and ear anomalies syndrome (CHARGE) and idiopathic scoliosis. Monosomy of 15q26 also has been associated with a spectrum of congenital abnormalities and growth retardation that overlaps with those of DGAP025. To provide a biological correlate, we characterized a mutant mouse model with Chd2 disruption that is associated with embryonic and perinatal lethality. Expression analysis indicated that Chd2 is expressed in the heart, forebrain, extremities, facial and dorsal regions during specific times of embryonic development. CM2(+/m) mice showed pronounced lordokyphosis, reduced body fat, postnatal runting, and growth retardation. These data suggest that haploinsufficiency for CHD2 could result in a complex of abnormal human phenotypes that includes scoliosis and possibly features similar to CHARGE syndrome. (C) 2008 Wiley-Liss, Inc.