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Abstract：
Johanson-Blizzard syndrome (JBS) is a rare genetic disorder caused by Ubiquitin Protein Ligase E3 Component N-Recognin1 (UBR1) gene mutations. It is characterized by exocrine pancreatic insufficiency, craniofacial deformities, sensorineural hearing loss, and a broad variety of intellectual disabilities. The aim of our study is to report four pediatric cases (three of which are siblings, and the fourth patient is unrelated) that presented some features of JBS. The cases have been confirmed by genetic testing to have mutations in the UBR1 gene. This case series study was conducted retrospectively, giving a detailed description of the demographic and clinical information of these four cases, and reflecting our experience with this subset of patients. All these cases have been treated at the King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia, and were identified by their clinical and laboratory markers that favor JBS. A novel homozygous missense mutation c.2075 T > C (p. lle692Thr) in exon 18 (UBR1: NM_174916.3) was identified and confirmed by Sanger sequencing in all our cases outlined in this paper. These presented cases illustrate the phenotypic variability and complexity of JBS and the importance of physical examination to reach a diagnosis. The identified novel mutation in this study broadens the spectrum of UBR1 mutations that contribute to JBS.
摘要：
Johanson-Blizzard综合征（JBS）是一种罕见的遗传性疾病，由泛素蛋白连接酶E3成分N-Recognin1（UBR1）基因突变引起。它的特点是胰腺外分泌功能不全，颅面畸形,感觉神经性听力损失,和各种各样的智力障碍。我们研究的目的是报告四例儿科病例（其中三例是兄弟姐妹，和第四例患者无关），表现出JBS的一些特征。这些病例已通过基因检测证实UBR1基因突变。这项病例系列研究是回顾性进行的，详细描述了这四个病例的人口统计学和临床信息，并反映了我们对这部分患者的经验。所有这些病例均已在费萨尔国王专科医院及研究中心接受治疗,吉达,沙特阿拉伯,并通过其支持JBS的临床和实验室标志物进行鉴定。一种新的纯合错义突变c.2075T>C（p。在本文概述的所有病例中，通过Sanger测序鉴定并确认了外显子18（UBR1：NM_174916.3）中的lle692Thr）。这些病例说明了JBS的表型变异性和复杂性以及体格检查对诊断的重要性。本研究中鉴定的新突变拓宽了有助于JBS的UBR1突变谱。
