SON基因异常致ZTTK综合征3例临床及遗传学分析
Clinical features of three patients with ZTTK syndrome caused by SON gene mutation
Received date: 2022-02-05
Online published: 2023-02-16
目的 探讨SON基因变异所致的ZTTK综合征（Zhu-Tokita-Takenouchi-Kim syndrome）患儿的临床表现及基因变异特点。方法 回顾性分析3例ZTTK综合征的临床资料。应用全外显子测序技术（WES）对患者进行基因变异分析，Sanger测序技术对变异位点进行验证。结果 3例患儿，年龄10个月~3岁8个月，临床表型为面容异常、发育落后、智力低下、小头畸形、肌张力异常;手关节异常或足外翻，肾盂肾炎、隐睾以及颅缝早闭等症状。其中两例患儿头颅MRI可见脑沟增宽、脑发育不良等异常。WES检测发现3例患儿SON基因均存在变异，分别为c.3020G>A（p.R1007H）、c.1195delG （p.V399fsTer1）以及c.5753_5756delTTAG （p.V1918EfsTer87），其父母均未见异常。结论 3例SON基因异常所致的ZTTK综合征，扩展了该基因的突变谱。SON基因变异导致的ZTTK综合征临床表现为多系统受累;WES可帮助临床明确诊断。
赵培伟 , 毕博 , 张蕾 , 黄玉凤 , 谭黎 , 何学莲 , 朱红敏 . SON基因异常致ZTTK综合征3例临床及遗传学分析[J]. 临床儿科杂志, 2023 , 41(2) : 113 -116 . DOI: 10.12372/jcp.2023.22e0180
Objective To investigate the clinical features and gene mutation of patients diagnosed with ZTTK syndrome (Zhu-Tokita-Takenouchi-Kim syndrome). Method The clinical data of three cases of ZTTK syndrome were retrospectively analyzed. Whole exome sequencing was applied to analyze the patients' genetic variants, and Sanger sequencing was used to verify the variant loci. Results In this study, 3 patients, aged from 10 months to 3 years and 8 months, had clinical phenotypes of facial dysmorphism, developmental delay, intellectual disability, microcephaly and abnormal muscle tone, abnormal hand joint or foot valgus, pyelonephritis, cryptorchidism and premature closure of cranial suture. In two cases, sulcus widening and cerebral dysplasia were observed on brain MRI. We found de novo variation in SON gene in all three children, c.3020G>A (p.R1007H), c.1195delG (p.V399fsTer1) and c.5753_5756delTTAG (p.V1918EfsTer87). Conclusion This study reports three cases of ZTTK syndrome due to SON gene abnormalities, which expands the mutation spectrum of SON gene. In this paper, we report three cases of ZTTK syndrome, extending the spectrum of mutations in this gene. The clinical manifestations of ZTTK syndrome are of multisystem involvement; whole exome sequencing may help to make a clear clinical diagnosis.
Key words： ZTTK syndrome; SON gene; whole exome sequencing; gene mutation
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