SHANK3新突变导致Phelan-McDermid综合征4例临床及遗传学特点分析

Clinical and genetic characteristics analysis of four cases of Phelan-McDermid syndrome caused by the novel mutations of the SHANK3 gene

收集2014年1月至2019年10月北京大学第一医院儿科门诊收治的4例Phelan-McDermid综合征(PMS)患儿基本信息、临床资料, 采用全外显子测序技术对患儿家系进行检测, 总结分析患儿的临床及遗传学特点, 并进行基因型-表型分析。4例患儿均表现为发育迟缓, 尤其是语言发育落后, 例2有孤独症样表现。基因检测结果发现4种SHANK3变异:c.2861delC p.(S955Pfs*109)、c.3166delC p.(A1039Afs*39)、c.3711;723delGCCCAGCCCCCGG p.(L1241Lfs*29)和c.2223+1G>A, 经美国医学遗传学与基因组学学会致病性评级均为致病性, 为未报道的新变异。本研究扩展了SHANK3突变谱, 为PMS准确的遗传咨询及产前诊断提供了实验依据。

The basic information and clinical data of 4 Phelan-McDermid syndrome(PMS)patients in the Pediatric Outpatient Department of the Peking University First Hospital from January 2014 to October 2019 were retrospectively analyzed.Genetic diagnoses were performed using the whole exon sequencing assay.The genotype-phenotype correlation analysis was then performed.All patients presented with intellectual disability/developmental delay,especially the most-common manifestation in language disability.Patient 2 had an autism behavior.Four novel variations of the SHANK3 gene were found in this study,including the c.2861delC p.(S955Pfs*109),c.3166delC p.(A1039Afs*39),c.3711_3723delGCCCAGCCCCCGG p.(L1241Lfs*29)and c.2223+1G>A.All of them were analyzed as new pathogenic variations according to the American College of Medical Genetics and Genomics criteria.The present study expan-ded the mutant spectrum of the SHANK3 gene,which provided a basis for further accurate genetic counseling and prenatal diagnosis of PMS.