Lyon Sarah M, Waggoner Darrel, Halbach Sara, Thorland Erik C, Khorasani Leila, Reid Russell R
Pritzker School of Medicine, University of Chicago.
Department of Human Genetics and Pediatrics, University of Chicago, 5841 S. Maryland Ave, M/C 0077, Chicago, IL 60637.
Genes Dis. 2015 Dec;2(4):347-352. doi: 10.1016/j.gendis.2015.09.001. Epub 2015 Sep 21.
Craniosynostosis, a condition in which the cranial sutures prematurely fuse, can lead to elevated intracranial pressure and craniofacial abnormalities in young children. Currently surgical intervention is the only therapeutic option for patients with this condition. Craniosynostosis has been associated with a variety of different gene mutations and chromosome anomalies. Here we describe three cases of partial deletion of chromosome 19p. Two of the cases present with syndromic craniosynostosis while one has metopic ridging. A review of the genes involved in the rearrangements between the three cases suggests several gene candidates for craniosynostosis. CALR and DAND5, BMP regulators involved in osteoblast differentiation, and MORG1, a mediator of osteoclast dysregulation may play a role in abnormal cranial vault development. Additionally, CACNA1A, a gene that when mutated is associated with epilepsy and CC2D1A, a gene associated with nonsyndromic mental retardation may contribute to additional phenotypic features seen in the patients we describe. In addition, these findings further support the need for genetic testing in cases of syndromic craniosynostosis.
颅缝早闭是一种颅缝过早融合的疾病,可导致幼儿颅内压升高和颅面异常。目前,手术干预是患有这种疾病的患者唯一的治疗选择。颅缝早闭与多种不同的基因突变和染色体异常有关。在这里,我们描述了三例19号染色体短臂部分缺失的病例。其中两例表现为综合征性颅缝早闭,而另一例有额缝隆起。对这三例病例中涉及重排的基因进行回顾,提示了几个可能与颅缝早闭相关的候选基因。参与成骨细胞分化的骨膜蛋白调节因子CALR和DAND5,以及破骨细胞失调的介质MORG1可能在颅穹窿异常发育中起作用。此外,一个突变时与癫痫相关的基因CACNA1A和一个与非综合征性智力迟钝相关的基因CC2D1A可能导致我们所描述患者出现的其他表型特征。此外,这些发现进一步支持了对综合征性颅缝早闭病例进行基因检测的必要性。