Characterization of a new syndrome that associates craniosynostosis, delayed fontanel closure, parietal foramina, imperforate anus, and skin eruption: CDAGS
Characterization of a new syndrome that associates craniosynostosis, delayed fontanel closure, parietal foramina, imperforate anus, and skin eruption: CDAGS
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DOI：
10.1086/431654
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发表时间：
2005-07-01
影响因子：
9.8
通讯作者：
Lee, B
中科院分区：
文献类型：
--
作者：
Mendoza-Londono, R;Lammer, E;Lee, B
我们描述了一种独特的遗传病的临床特征、分子分析和基因定位，这种疾病的特征为颅缝早闭、囟门延迟闭合、颅骨缺损、锁骨发育不全、肛门和泌尿生殖系统畸形以及皮疹。我们在来自不同地理区域和种族背景的四个家庭中确定了七名具有这种表型的患者。这是一种常染色体隐性遗传病，它包含了明显相反的病理生理和发育过程，包括加速的骨缝闭合和延迟的骨化。通过对其编码区直接测序筛选了选定的候选基因（包括RUNX2、CBFB、MSX2、ALX4、TWIST1和RECQL4）的突变，并通过荧光原位杂交筛选了微小缺失。在所分析的任何基因中均未检测到突变或微小缺失。全基因组筛查得出染色体22q12 - q13上的标记D22S283和D22S274的最大估计对数优势计分（LOD score）为+2.38。我们假设这种疾病的基因缺陷在成骨细胞分化和颅面形态发生过程中导致包括RUNX2在内的多个信号通路出现新的依赖于环境的失调。
We describe the clinical characterization, molecular analyses, and genetic mapping of a distinct genetic condition characterized by craniosynostosis, delayed closure of the fontanel, cranial defects, clavicular hypoplasia, anal and genitourinary malformations, and skin eruption. We have identified seven patients with this phenotype in four families from different geographic regions and ethnic backgrounds. This is an autosomal recessive condition that brings together apparently opposing pathophysiologic and developmental processes, including accelerated suture closure and delayed ossification. Selected candidate genes - including RUNX2, CBFB, MSX2, ALX4, TWIST1, and RECQL4 - were screened for mutations, by direct sequencing of their coding regions, and for microdeletions, by fluorescent in situ hybridization. No mutations or microdeletions were detected in any of the genes analyzed. A genomewide screen yielded the maximum estimated LOD score of + 2.38 for markers D22S283 and D22S274 on chromosome 22q12- q13. We hypothesize that the gene defect in this condition causes novel context- dependent dysregulation of multiple signaling pathways, including RUNX2, during osteoblast differentiation and craniofacial morphogenesis.