摘要目的:探讨4例Phelan-McDermid综合征(PMS)患儿的临床特征与遗传学病因。方法:选取2022年6月2日至2023年5月8日在宁波大学附属妇女儿童医院就诊的4例PMS患儿为研究对象。收集患儿的临床资料，采集患儿及其父母的外周血样，提取DNA，进行全外显子组测序(WES)，并通过Sanger测序和荧光定量PCR(q-PCR)技术对候选变异进行验证。本研究通过宁波大学附属妇女儿童医院医学伦理委员会的审查(伦理号：EC2020-048)。结果:4例患儿均表现为语言发育迟缓和智力障碍，患儿3和4具有自闭症表现。患儿1和2分别携带 SHANK3基因c.731T>C(p.Leu244Pro)和c.2782_2851del(p.Gly928ArgfsTer4)杂合变异，经Sanger测序验证其父母均未携带上述变异，提示为新发变异。患儿3和4在22q13.33区分别存在121 kb和52.02 kb的杂合缺失，均涉及 SHANK3和 ACR基因，经q-PCR验证，2例患儿均存在 SHANK3和 ACR基因杂合缺失，其父母均无缺失，提示为新发变异。根据美国医学遗传学与基因组学学会相关指南， SHANK3基因c.731T>C和c.2782_2851del分别被评定为可能致病性变异(PS2＋PM2_Supporting＋PP3)和致病性变异(PVS1＋PM2_Supporting＋PS2_Supporting)；染色体22q13.33区段52.02 kb和121 kb的杂合缺失均被评定为致病性变异(2D＋4C，赋值1.05分；2D＋4C，赋值1分)。 结论:本研究通过基因检测确诊了4例PMS患儿，丰富了PMS的变异谱和表型谱，为患儿的临床诊断和遗传咨询提供了依据。

abstractsObjective:To explore the clinical characteristics and genetic etiology of four children with Phelan-McDermid syndrome (PMS).Methods:Four children who had visited the Affiliated Women and Children′s Hospital of Ningbo University between June 2, 2022 and May 8, 2023 were selected as the study subjects. Clinical data of the children were collected. Genomic DNA was extracted from peripheral blood samples of the children and their parents and subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing and quantitative PCR (q-PCR) analysis. This study was approved by the Medical Ethics Committee of the Affiliated Women and Children′s Hospital of Ningbo University (Ethics No. EC2020-048).Results:All children had presented with speech and language delays and intellectual disability. Children 3 and 4 also presented with autistic behaviors. WES showed that the children 1 and 2 had respectively carried a heterozygous c.731T>C (p.Leu244Pro) and a c.2782_2851del (p.Gly928ArgfsTer4) variant of the SHANK3 gene. Sanger sequencing confirmed that their parents did not carry the same variant, suggesting that they were de novo in origin. Children 3 and 4 had respectively harbored a 121 kb and 52.02 kb heterozygous deletion at chromosome 22q13.33, which had both encompassed the SHANK3 and ACR genes mapped to 22q13.33. q-PCR results showed that the deletion of SHANK3 and ACR genes were de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 731T>C and c. 2782_2851del variants were predicted to be likely pathogenic (PS2+ PM2_Supporting+ PP3) and pathogenic (PVS1+ PM2_Supporting+ PS2_Supporting), respectively. Furthermore, the 52.02 kb and 121 kb heterozygous deletions in 22q13.33 were both predicted to be pathogenic (2D+ 4C, 1.05 in score; 2D+ 4C, 1 in score). Conclusion:The four children were all diagnosed with PMS by genetic testing. Above finding has enriched the phenotypic and mutational spectrum of PMS, and provided a basis for clinical diagnosis and genetic counseling for their families.