SON基因异常致ZTTK综合征3例临床及遗传学分析

doi:10.12372/jcp.2023.22e0180

摘要/Abstract

摘要：

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。

关键词: ZTTK综合征, SON基因, 全外显子测序, 基因变异

Abstract:

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

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.

ZHAO Peiwei, BI Bo, ZHANG Lei, HUANG Yufeng, TAN Li, HE Xuelian, ZHU Hongmin. Clinical features of three patients with ZTTK syndrome caused by SON gene mutation[J]. Journal of Clinical Pediatrics, 2023, 41(2): 113-116.

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参考文献 20

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项目	P1	P2	P3
性别	男	女	男
年龄	10月龄	3岁8个月	13月龄
身高/cm	75	85(－3SD)	75
体重/kg	10.5	9.5(－3SD)	9
头围/cm	42(－2SD)	ND	45
面容异常	小头畸形	眼睑下斜，招风耳	未见明显异常
发育迟缓	+	+	+
智力低下	+	+	+
癫痫	未见发作	未见发作	未见发作
头颅MRI异常	双侧大脑半球白质内异常信号，白质脑病多考虑;左侧大脑半球容积较小，脑沟宽，脑发育不良多考虑	ND	双侧颞部脑外间隙稍宽，大枕大池，双侧侧脑室扩大;顶部头皮血肿
肌张力	肌张力低下	肌张力偏低	肌张力偏低
眼睛异常	无	无	斜视
骨骼畸形	双足扁平外翻，右足明显	双手关节形态异常,足外翻	双足扁平外翻，颅缝早闭，脊柱侧弯
泌尿生殖系统	未见明显异常	急性肾盂肾炎，右侧输尿管下段轻度增宽	双侧腹股沟斜疝，隐睾
其他异常	右侧听力功能障碍	脓毒血症，轻度贫血	颅缝早闭
SON基因变异（NM_138927）	c.3020G>A p.R1007H	c.1195delG p.V399fsTer1	c.5753_5756delTTAG p.V1918EfsTer87