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Novel PCNT variants in MOPDII with attenuated growth restriction and pachygyria.
Clinical Genetics ( IF 2.9 ) Pub Date : 2020-06-17 , DOI: 10.1111/cge.13797 Stephanie Waich 1, 2 , Andreas R Janecke 1, 3 , Walther Parson 4, 5 , Susanne Greber-Platzer 2 , Thomas Müller 1 , Lukas A Huber 6 , Taras Valovka 1 , Julia Vodopiutz 2
Clinical Genetics ( IF 2.9 ) Pub Date : 2020-06-17 , DOI: 10.1111/cge.13797 Stephanie Waich 1, 2 , Andreas R Janecke 1, 3 , Walther Parson 4, 5 , Susanne Greber-Platzer 2 , Thomas Müller 1 , Lukas A Huber 6 , Taras Valovka 1 , Julia Vodopiutz 2
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Biallelic loss‐of‐function mutations in the centrosomal pericentrin gene (PCNT) cause microcephalic osteodysplastic primordial dwarfism type II (MOPDII), which is characterized by extreme growth retardation, microcephaly, skeletal dysplasia, and dental anomalies. Life expectancy is reduced due to a high risk of cerebral vascular anomalies. Here, we report two siblings with MOPDII and attenuated growth restriction, and pachygyria. Compound heterozygosity for two novel truncated PCNT variants was identified. Both truncated PCNT proteins were expressed in patient's fibroblasts, with a reduced total protein amount compared to control. Patient's fibroblasts showed impaired cell cycle progression. As a novel finding, 20% of patient's fibroblasts were shown to express PCNT comparable to control. This was associated with normal mitotic morphology and normal co‐localization of mutated PCNT with centrosome‐associated proteins γ‐tubulin and centrin 3, suggesting some residual function of truncated PCNT proteins. These data expand the clinical and molecular spectrum of MOPDII and indicate that residual PCNT function might be associated with attenuated growth restriction in MOPDII.
中文翻译：
MOPDII中新的PCNT变异体具有减缓的生长限制和短绒毛膜。
中心体周质蛋白基因（PCNT）中的双等位基因功能丧失突变会导致II型小头畸形原发性侏儒症（MOPDII），其特征是极度的发育迟缓，小头畸形，骨骼发育不良和牙齿异常。由于存在脑血管异常的高风险，预期寿命会缩短。在这里，我们报告了MOPDII的两个兄弟姐妹和减慢的生长限制以及后坐垫。两个新型截短的PCNT的复合杂合性确定了变体。两种截短的PCNT蛋白均在患者的成纤维细胞中表达，与对照组相比，总蛋白量减少。患者的成纤维细胞显示细胞周期进程受损。作为一项新发现，显示患者20％的成纤维细胞可表达与对照相当的PCNT。这与正常的有丝分裂形态和突变的PCNT与中心体相关蛋白γ-微管蛋白和centrin 3的正常共定位有关，这表明截短的PCNT蛋白具有某些残留功能。这些数据扩展了MOPDII的临床和分子谱，并表明残留的PCNT功能可能与MOPDII的生长受限减弱有关。
更新日期：2020-06-17
中文翻译：
MOPDII中新的PCNT变异体具有减缓的生长限制和短绒毛膜。
中心体周质蛋白基因（PCNT）中的双等位基因功能丧失突变会导致II型小头畸形原发性侏儒症（MOPDII），其特征是极度的发育迟缓，小头畸形，骨骼发育不良和牙齿异常。由于存在脑血管异常的高风险，预期寿命会缩短。在这里，我们报告了MOPDII的两个兄弟姐妹和减慢的生长限制以及后坐垫。两个新型截短的PCNT的复合杂合性确定了变体。两种截短的PCNT蛋白均在患者的成纤维细胞中表达，与对照组相比，总蛋白量减少。患者的成纤维细胞显示细胞周期进程受损。作为一项新发现，显示患者20％的成纤维细胞可表达与对照相当的PCNT。这与正常的有丝分裂形态和突变的PCNT与中心体相关蛋白γ-微管蛋白和centrin 3的正常共定位有关，这表明截短的PCNT蛋白具有某些残留功能。这些数据扩展了MOPDII的临床和分子谱，并表明残留的PCNT功能可能与MOPDII的生长受限减弱有关。
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