Raynaud-Claes综合征患儿1例的CLCN4基因变异分析

Analysis of CLCN4 gene variant in a child with Raynaud-Claes syndrome

目的分析1例CLCN4基因变异所致Raynaud-Claes综合征(RCS)患儿的临床表型和基因变异情况,为该病的诊断提供参考。方法选取2022年8月因"语言与运动较同龄儿落后"于郑州大学附属儿童医院康复医学科门诊的1例RCS男性患儿为研究对象。采集患儿临床资料,应用目标捕获高通量测序和Sanger测序技术对患儿及其父母进行基因变异检测,并对候选变异进行致病性分析。结果患儿为4岁4个月男性,表现为全面发育迟缓、言语障碍、特殊面容及行为异常。基因检测结果提示患儿CLCN4基因存在c.1174C>T(p.Gln392Ter)半合子变异,其父母均未携带该变异,提示为新发变异。根据美国医学遗传学与基因组学学会(ACMG)相关指南,该变异被评定为致病性变异(PVS1+PS2+PM2_Supporting)。结论CLCN4基因c.1174C>T(p.Gln392Ter)新发变异可能是本研究患儿的遗传致病原因,该变异的发现进一步扩大了RCS的致病基因变异谱,为该家系遗传咨询及产前诊断提供依据。

Objective To analyze the clinical phenotype and genetic variant in a child with Raynaud-Claes syndrome(RCS).Methods A child who was diagnosed with RCS at the Children′s Hospital Affiliated to Zhengzhou University for delayed language and motor development in August 2022 was selected as the study subject.Clinical data of the child were collected,and potential genetic variant was detected by next-generation sequencing and Sanger sequencing.The pathogenicity of the candidate variant was analyzed.Results The child,a 4-year-and-4-month-old male,has manifested global developmental delay,speech disorders,special facial features and behavioral abnormalities.Genetic testing revealed that he has harbored a hemizygous c.1174C>T(p.Gln392Ter)variant of the CLCN4 gene,which was not detected in either of his parents.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),the variant was rated as pathogenic(PVS1+PS2+PM2_Supporting).Conclusion The c.1174C>T(p.Gln392Ter)variant of the CLCN4 gene probably underlay the PCS in this child.Above finding has expanded the mutational spectrum of the CLCN4 gene and enabled genetic counseling and prenatal diagnosis for his family.