·113·临床儿科杂志2023年第41卷第2期JClinPediatrVol.41No.2Feb.2023SON基因异常致ZTTK综合征3例临床及遗传学分析赵培伟毕博张蕾黄玉凤谭黎何学莲朱红敏华中科技大学同济医学院附属武汉儿童医院（湖北武汉430016）摘要：目的探讨SON基因变异所致的ZTTK综合征（Zhu-Tokita-Takenouchi-Kimsyndrome）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ClinicalfeaturesofthreepatientswithZTTKsyndromecausedbySONgenemutationZHAOPeiwei,BIBo,ZHANGLei,HUANGYufeng,TANLi,HEXuelian,ZHUHongmin(WuhanChildren'sHospital,TongjiMedicalCollege,HuazhongUniversityofScience&Technology,Wuhan430016,Hubei,China)Abstract:ObjectiveToinvestigatetheclinicalfeaturesandgenemutationofpatientsdiagnosedwithZTTKsyndrome(Zhu-Tokita-Takenouchi-Kimsyndrome).MethodTheclinicaldataofthreecasesofZTTKsyndromewereretrospectivelyanalyzed.Wholeexomesequencingwasappliedtoanalyzethepatients'geneticvariants,andSangersequencingwasusedtoverifythevariantloci.ResultsInthisstudy,3patients,agedfrom10monthsto3yearsand8months,hadclinicalphenotypesoffacialdysmorphism,developmentaldelay,intellectualdisability,microcephalyandabnormalmuscletone,abnormalhandjointorfootvalgus,pyelonephritis,cryptorchidismandprematureclosureofcranialsuture.Intwocases,sulcuswideningandcerebraldysplasiawereobservedonbrainMRI.WefounddenovovariationinSONgeneinallthreechildren,c.3020G>A(p.R1007H),c.1195delG(p.V399fsTer1)andc.5753_5756delTTAG(p....
