Department of Oral and Maxillofacial Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
Department of Molecular Life Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
BMC Med Genet. 2019 Jul 16;20(1):126. doi: 10.1186/s12881-019-0858-z.
Osteodysplasia of the oral and maxillofacial bone is generally accompanied by systemic bone abnormalities (such as short stature, joint contracture) or other systemic abnormalities (such as renal, dermatological, cardiovascular, optic, or hearing disorders). However, it does not always present this way. Recent reports have suggested that genome-wide sequencing is an effective method for identifying rare or new disorders. Here, we performed whole-exome sequencing (WES) in a patient with a unique form of acquired, local osteodysplasia of the oral and maxillofacial region.
A 46-year-old woman presented to our hospital with the complaint of gradually moving mandibular teeth (for 6 months), changing facial appearance, and acquired osteolysis of the oral and maxillofacial bones, showing mandibular hypoplasia without family history. Upon skeletal examination, there were no abnormal findings outside of the oral and maxillofacial area; the patient had a height of 157 cm and bone mineral density (according to dual energy x-ray absorptiometry) of 90%. Results of blood and urine tests, including evaluation of bone metabolism markers and neurological and cardiovascular examinations, were normal. We performed WES of genomic DNA extracted from the blood of this patient and her mother, who did not have the disease, as a negative control. We identified 83 new missense variants in the patient, not detected in her mother, including a candidate single nucleotide variant in exon 14 of PCNT (pericentrin). Critical homozygous or compound heterozygous variants in PCNT are a known cause of microcephalic osteodysplastic primordial dwarfism type II accompanied by mandibular hypoplasia, which is similar to the maxillofacial phenotype in this patient.
Protein simulations performed using Polymorphism Phenotyping v2 and Combined Annotation Dependent Depletion software indicated that this missense variant is likely to disrupt the PCNT protein structure. These results suggest that this is a new form of osteolysis related to this PCNT variant.
口腔颌面部骨的骨发育不良通常伴有全身骨骼异常（如身材矮小、关节挛缩）或其他全身异常（如肾、皮肤、心血管、视觉或听觉障碍）。然而，它并不总是这样表现。最近的报告表明，全基因组测序是识别罕见或新疾病的有效方法。在这里，我们对一名患有口腔颌面部局部获得性骨发育不良的患者进行了全外显子组测序（WES）。
一名 46 岁女性因逐渐移动的下颌牙齿（6 个月）、面部改变和口腔颌面部获得性骨溶解来到我院就诊，表现为下颌骨发育不良，无家族史。骨骼检查除口腔颌面部外无异常发现；患者身高 157cm，骨密度（根据双能 X 线吸收法）为 90%。血液和尿液检查结果正常，包括骨代谢标志物评估、神经和心血管检查。我们对该患者和未患病的母亲的血液基因组 DNA 进行了 WES，作为阴性对照。我们在患者中发现了 83 个新的错义变异，未在其母亲中检测到，包括 PCNT（中心体蛋白）外显子 14 中的一个候选单核苷酸变异。PCNT 关键纯合或复合杂合变异是小头性骨发育不良原基性侏儒症 II 型的已知原因，伴有下颌骨发育不良，与该患者的颌面表型相似。
使用 Polymorphism Phenotyping v2 和 Combined Annotation Dependent Depletion 软件进行的蛋白质模拟表明，这种错义变异可能会破坏 PCNT 蛋白结构。这些结果表明，这是一种与该 PCNT 变异相关的新形式的骨溶解。
