全外显子组测序有助于诊断4例中国儿童的Joubert综合征相关疾病。
Whole exome sequencing facilitated the diagnosis in four Chinese pediatric cases of Joubert syndrome related disorders.
作者信息
Zhang Jing, Wang Lihui, Chen Wenqi, Duan Jun, Meng Yanxin, Yang Huafang, Guo Qing
机构信息
Prenatal Diagnosis Center, Shijiazhuang Obstetrics and Gynecology Hospital, Hebei Medical University (Key Laboratory of Maternal and Fetal Medicine of Hebei Province) Shijiazhuang, Hebei, China.
Neurology Department, Children's Hospital of Hebei Province, Hebei Medical University Shijiazhuang, Hebei, China.
出版信息
Am J Transl Res. 2022 Jul 15;14(7):5088-5097. eCollection 2022.
OBJECTIVES
Joubert syndrome is a spectrum of rare genetic disorders, mainly characterized by a distinctive cerebellar and brain stem malformation called the "molar tooth sign" (MTS), hypotonia, and intellectual disability/developmental delay.
METHODS
In this study, 4 pediatric cases with developmental delay and oculomotor abnormities were recruited, and submitted to a clinical evaluation and magnetic resonance imaging (MRI) examination. Afterwards, genetic detection with whole exome sequencing (WES) was conducted on the 4 patients.
RESULTS
Imaging results demonstrated cerebellar dysplasia in all probands, yet the MTS findings varied in severity. WES detected diagnostic variations in all four probands, which were distributed in four genes, namely , and . Two variants were novelly identified, which were the : c.2444delC (p.P815fs*2) and the : exon (15-17) del. analysis supported the pathogenicity of the variations in this study.
CONCLUSIONS
Our findings expanded the mutation spectrum of Joubert syndrome related disorders, and provided solid evidence to the affected families for further genetic counseling and pregnancy guidance.
目的
乔伯特综合征是一系列罕见的遗传疾病，主要特征为一种独特的小脑和脑干畸形，称为“磨牙征”（MTS）、肌张力减退以及智力残疾/发育迟缓。
方法
本研究招募了4例有发育迟缓及眼球运动异常的儿科病例，并对其进行临床评估和磁共振成像（MRI）检查。之后，对这4例患者进行全外显子组测序（WES）基因检测。
结果
影像学结果显示所有先证者均存在小脑发育异常，但MTS表现的严重程度各异。WES在所有4例先证者中均检测到诊断性变异，这些变异分布于4个基因，即 、 和 。新发现了2个变异，分别为 ：c.2444delC（p.P815fs*2）和 ：外显子（15 - 17）缺失。 分析支持了本研究中变异的致病性。
结论
我们的研究结果扩展了乔伯特综合征相关疾病的突变谱，并为受影响家庭提供了坚实依据，以便进行进一步的遗传咨询和妊娠指导。
Zotero 插件