Badri Mohammed K, Zhang Honghao, Ohyama Yoshio, Venkitapathi Sundharamani, Kamiya Nobuhiro, Takeda Haruko, Ray Manas, Scott Greg, Tsuji Takehito, Kunieda Tetsuo, Mishina Yuji, Mochida Yoshiyuki
Department of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine, Boston University, Boston, Massachusetts.
Department of Pediatric Dentistry and Orthodontics, College of Dentistry, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia.
Anat Rec (Hoboken). 2016 Aug;299(8):1110-20. doi: 10.1002/ar.23353. Epub 2016 May 2.
Ellis-van Creveld (EvC) syndrome is a genetic disorder with mutations in either EVC or EVC2 gene. Previous case studies reported that EvC patients underwent orthodontic treatment, suggesting the presence of craniofacial bone phenotypes. To investigate whether a mutation in EVC2 gene causes a craniofacial bone phenotype, Evc2 knockout (KO) mice were generated and cephalometric analysis was performed. The heads of wild type (WT), heterozygous (Het) and homozygous Evc2 KO mice (1-, 3-, and 6-week-old) were prepared and cephalometric analysis based on the selected reference points on lateral X-ray radiographs was performed. The linear and angular bone measurements were then calculated, compared between WT, Het and KO and statistically analyzed at each time point. Our data showed that length of craniofacial bones in KO was significantly lowered by ∼20% to that of WT and Het, the growth of certain bones, including nasal bone, palatal length, and premaxilla was more affected in KO, and the reduction in these bone length was more significantly enhanced at later postnatal time points (3 and 6 weeks) than early time point (1 week). Furthermore, bone-to-bone relationship to cranial base and cranial vault in KO was remarkably changed, i.e. cranial vault and nasal bone were depressed and premaxilla and mandible were developed in a more ventral direction. Our study was the first to show the cause-effect relationship between Evc2 deficiency and craniofacial defects in EvC syndrome, demonstrating that Evc2 is required for craniofacial bone development and its deficiency leads to specific facial bone growth defect. Anat Rec, 299:1110-1120, 2016. © 2016 Wiley Periodicals, Inc.
埃利斯-范克里维尔德综合征（EvC综合征）是一种由EVC或EVC2基因突变引起的遗传性疾病。以往的病例研究报告称，EvC综合征患者接受了正畸治疗，提示存在颅面骨表型。为了研究EVC2基因突变是否会导致颅面骨表型，研究人员构建了Evc2基因敲除（KO）小鼠并进行了头影测量分析。制备了野生型（WT）、杂合子（Het）和纯合Evc2基因敲除小鼠（1周龄、3周龄和6周龄）的头部，并基于侧位X线片上选定的参考点进行了头影测量分析。然后计算线性和角度骨测量值，在WT、Het和KO之间进行比较，并在每个时间点进行统计分析。我们的数据显示，KO小鼠的颅面骨长度比WT和Het小鼠显著降低了约20%，包括鼻骨、腭长度和上颌前部在内的某些骨骼的生长在KO小鼠中受到的影响更大，并且这些骨骼长度的减少在出生后较晚的时间点（3周和6周）比早期时间点（1周）更为显著。此外，KO小鼠中颅骨与颅底和颅顶之间的骨与骨关系发生了显著变化，即颅顶和鼻骨凹陷，上颌前部和下颌骨向更腹侧方向发育。我们的研究首次表明了EvC综合征中Evc2基因缺陷与颅面缺陷之间的因果关系，证明Evc2基因是颅面骨发育所必需的，其缺陷会导致特定的面部骨骼生长缺陷。《解剖学记录》，299:1110 - 1120，2016年。©2016威利期刊公司。
