Rossi-Espagnet Maria C, Dentici Maria L, Pasquini Luca, Carducci Chiara, Lucignani Martina, Longo Daniela, Agolini Emanuele, Novelli Antonio, Gonfiantini Michaela V, Digilio Maria C, Napolitano Antonio, Bartuli Andrea
Neuroradiology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Nesmos Department, Sapienza University, Rome, Italy.
Am J Med Genet A. 2020 Oct;182(10):2372-2376. doi: 10.1002/ajmg.a.61771. Epub 2020 Aug 3.
Microcephalic osteodysplastic primordial dwarfism (MOPD) type II is a rare disorder characterized by skeletal dysplasia, severe proportionate short stature, insulin resistance and cerebrovascular abnormalities including cerebral aneurysms and moyamoya disease. MOPD type II is caused by mutations in the pericentrin (PCNT) gene, which encodes a protein involved in centrosomes function. We report a 2 year old girl affected by MOPD type II caused by two compound heterozygous loss-of-function variants in PCNT gene, of which one is a novel variant (c.5304delT; p.Gly1769AlafsTer34). The patient presented atypical brain magnetic resonance imaging (MRI) findings consistent with pachygyria. This was confirmed by morphometric analysis of cortical thickness (CT) and gyrification index by comparing MRI data of the patient with a group of eight age-matched healthy controls. The statistical analysis revealed a significant and diffuse increase of CT with an anterior-predominant pattern and diffuse reduced gyrification (p < .05). These findings provide new evidences to the emergent concept that malformations of cortical development are complex disorders and that new genetic findings contribute to the fading of classification borders.
II型小头畸形性骨发育异常原发性侏儒症(MOPD)是一种罕见疾病,其特征为骨骼发育异常、严重的匀称性身材矮小、胰岛素抵抗以及包括脑动脉瘤和烟雾病在内的脑血管异常。II型MOPD由中心体蛋白(PCNT)基因突变引起,该基因编码一种参与中心体功能的蛋白质。我们报告了一名2岁女童,因PCNT基因中的两个复合杂合功能丧失变体而患II型MOPD,其中一个是新变体(c.5304delT;p.Gly1769AlafsTer34)。该患者的脑部磁共振成像(MRI)表现不典型,与巨脑回畸形一致。通过将患者的MRI数据与一组八名年龄匹配的健康对照者进行比较,对皮质厚度(CT)和脑回形成指数进行形态计量分析,证实了这一点。统计分析显示,CT显著且弥漫性增加,以前部为主,脑回形成弥漫性减少(p < 0.05)。这些发现为皮质发育畸形是复杂疾病以及新的基因发现导致分类界限逐渐模糊这一新兴概念提供了新证据。