{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T13:08:42Z","timestamp":1789391322664,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fujian Provincial Natural Science Foundation of China","award":["2022J01421"],"award-info":[{"award-number":["2022J01421"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Objectives: To characterize the clinical and genetic features of Phelan\u2013McDermid syndrome (PMS) in a Chinese prenatal and postnatal cohort, explore genotype\u2013phenotype correlations, and provide evidence to support prenatal genetic counseling. Methods: G-banded karyotyping, single-nucleotide polymorphism arrays (SNP arrays), copy number variation sequencing, and trio whole-exome sequencing were used for genetic diagnosis. Fifteen patients with PMS (11 prenatal and 4 postnatal) were retrospectively enrolled. Genomic visualization, protein structural prediction, and phenotypic heatmap analyses were conducted to analyze genotype\u2013phenotype associations. Results: The prenatal and postnatal detection rates of PMS were 0.061% and 0.49%, respectively. Only 13.3% of cases were detected by karyotyping, whereas 14 cases were confirmed by SNP array analysis. All 22q13 deletions (69.4 kb\u20138.5 Mb) involved SHANK3, and all copy number variants were de novo. A novel SHANK3 frameshift variant, c.3513_3514delCC, was identified and predicted to result in protein truncation leading to intellectual disability. Prenatal cases mainly presented non-specific ultrasound anomalies (63.6%, 7\/11), with fetal growth restriction, renal malformations, and cardiovascular defects being the most frequent findings. A notable 36.4% (4\/11) of prenatal cases were complicated by missed abortion, whereas postnatal patients showed predominant neurodevelopmental impairments. In our cohort, larger deletions were observed in cases presenting with more extensive multisystem involvement, a pattern that mirrors findings from recent large-cohort studies. central nervous system abnormalities were predominantly linked to SHANK3 haploinsufficiency, while multi-system malformations seemed to correlate with the cumulative loss of multiple genes across the 22q13 region, in keeping with current hypotheses on contiguous gene effects. Conclusions: PMS presents obvious prenatal\u2013postnatal phenotypic heterogeneity. SHANK3 is the core pathogenic gene, and deletion may influence the extent of multisystem involvement. Combined genetic testing can improve the accuracy of prenatal diagnosis and counseling for PMS.<\/jats:p>","DOI":"10.3390\/jcm15187130","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:09:51Z","timestamp":1789387791000},"page":"7130","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prenatal and Postnatal Identification of Phelan\u2013McDermid Syndrome in a Tertiary Referral Center: A 15-Case Series and Literature Review"],"prefix":"10.3390","volume":"15","author":[{"given":"Huili","family":"Xue","sequence":"first","affiliation":[{"name":"Medical Genetic Diagnosis and Therapy Center, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, No. 18 Daoshan Road, Gulou District, Fuzhou 350001, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Yifang","family":"Dai","sequence":"additional","affiliation":[{"name":"Medical Genetic Diagnosis and Therapy Center, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, No. 18 Daoshan Road, Gulou District, Fuzhou 350001, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Xianglan","family":"Ye","sequence":"additional","affiliation":[{"name":"College of Obstetrics, Gynecology and Pediatrics, Fujian Medical University, Wushan Campus, No. 88 Jiaotong Road, Taijiang District, Fuzhou 350001, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Obstetrics, Gynecology and Pediatrics, Fujian Medical University, Wushan Campus, No. 88 Jiaotong Road, Taijiang District, Fuzhou 350001, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Qun","family":"Guo","sequence":"additional","affiliation":[{"name":"Medical Genetic Diagnosis and Therapy Center, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, No. 18 Daoshan Road, Gulou District, Fuzhou 350001, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Na","family":"Lin","sequence":"additional","affiliation":[{"name":"Medical Genetic Diagnosis and Therapy Center, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, No. 18 Daoshan Road, Gulou District, Fuzhou 350001, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5775-5082","authenticated-orcid":false,"given":"Hailong","family":"Huang","sequence":"additional","affiliation":[{"name":"Medical Genetic Diagnosis and Therapy Center, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, No. 18 Daoshan Road, Gulou District, Fuzhou 350001, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8815-2735","authenticated-orcid":false,"given":"Liangpu","family":"Xu","sequence":"additional","affiliation":[{"name":"Medical Genetic Diagnosis and Therapy Center, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, No. 18 Daoshan Road, Gulou District, Fuzhou 350001, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104754","DOI":"10.1016\/j.ejmg.2023.104754","article-title":"Definition and clinical variability of SHANK3-related Phelan-McDermid syndrome","volume":"66","author":"Lapunzina","year":"2023","journal-title":"Eur. J. Med. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Drapeau, E., Riad, M., Kajiwara, Y., and Buxbaum, J.D. (2018). Behavioral Phenotyping of an Improved Mouse Model of Phelan-McDermid Syndrome with a Complete Deletion of the Shank3 Gene. eNeuro, 5.","DOI":"10.1101\/278622"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1891\/0730-0832.36.2.98","article-title":"Phelan-McDermid Syndrome","volume":"36","author":"Omansky","year":"2017","journal-title":"Neonatal Netw."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1002\/dneu.22128","article-title":"The emerging role of SHANK genes in neuropsychiatric disorders","volume":"74","author":"Guilmatre","year":"2014","journal-title":"Dev. Neurobiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"D1243","DOI":"10.1093\/nar\/gkae974","article-title":"The UCSC Genome Browser database: 2025 update","volume":"53","author":"Perez","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/ng1933","article-title":"Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders","volume":"39","author":"Durand","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/nrn.2016.183","article-title":"SHANK proteins: Roles at the synapse and in autism spectrum disorder","volume":"18","author":"Monteiro","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41431-017-0042-x","article-title":"Identification of 22q13 genes most likely to contribute to Phelan McDermid syndrome","volume":"26","author":"Mitz","year":"2018","journal-title":"Eur. J. Hum. Genet. EJHG"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1136\/jmg.40.8.575","article-title":"Molecular characterisation of the 22q13 deletion syndrome supports the role of haploinsufficiency of SHANK3\/PROSAP2 in the major neurological symptoms","volume":"40","author":"Wilson","year":"2003","journal-title":"J. Med. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Cammarata-Scalisi, F., Callea, M., Martinelli, D., Willoughby, C.E., Tadich, A.C., Araya Castillo, M., Lacruz-Rengel, M.A., Medina, M., Grimaldi, P., and Bertini, E. (2022). Clinical and Genetic Aspects of Phelan-McDermid Syndrome: An Interdisciplinary Approach to Management. Genes, 13.","DOI":"10.3390\/genes13030504"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Nevado, J., Garc\u00eda-Mi\u00f1a\u00far, S., Palomares-Bralo, M., Vallesp\u00edn, E., Guill\u00e9n-Navarro, E., Rosell, J., Bel-Fenell\u00f3s, C., Mori, M.\u00c1., Mil\u00e1, M., and del Campo, M. (2022). Variability in Phelan-McDermid Syndrome in a Cohort of 210 Individuals. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.652454"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13229-024-00619-z","article-title":"Phenome-wide profiling identifies genotype-phenotype associations in Phelan-McDermid syndrome using family-sourced data from an international registry","volume":"15","author":"Yin","year":"2024","journal-title":"Mol. Autism"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Sandoni, L., Chehbani, F., Asta, L., Camia, M., Ricciardello, A., Tomaiuolo, P., Cucinotta, F., Turriziani, L., Boncoddo, M., and Bellomo, F. (2026). Chromosome 22q13 terminal deletion size is associated with relevant clinical features in a sample of 63 Italian patients with Phelan-McDermid syndrome. J. Neurodev. Disord.","DOI":"10.1186\/s11689-026-09708-x"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1136\/jmedgenet-2011-100225","article-title":"Association between deletion size and important phenotypes expands the genomic region of interest in Phelan-McDermid syndrome (22q13 deletion syndrome)","volume":"48","author":"Sarasua","year":"2011","journal-title":"J. Med. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1002\/ajmg.a.62222","article-title":"Genotype-phenotype correlation in Phelan-McDermid syndrome: A comprehensive review of chromosome 22q13 deleted genes","volume":"185","author":"Ricciardello","year":"2021","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Hao, Y., Liu, Y., Yang, J., Li, X., Luo, F., Geng, Q., Li, S., Li, P., Wu, W., and Xie, J. (2022). Prenatal and postnatal diagnosis of Phelan-McDermid syndrome: A report of 21 cases from a medical center and review of the literature. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.961196"},{"key":"ref_17","first-page":"2145701","article-title":"The Necessity of Prenatal Diagnosis by CMA for the Women with NIPS-Positive Results","volume":"2020","author":"Xu","year":"2020","journal-title":"Int. J. Genom."},{"key":"ref_18","first-page":"245","article-title":"Technical standards for the interpretation and reporting of constitutional copy-number variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)","volume":"22","author":"Riggs","year":"2020","journal-title":"Genet. Med. Off. J. Am. Coll. Med. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_20","first-page":"1054","article-title":"Modeling the ACMG\/AMP variant classification guidelines as a Bayesian classification framework","volume":"20","author":"Tavtigian","year":"2018","journal-title":"Genet. Med. Off. J. Am. Coll. Med. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/978-1-4939-3578-9_16","article-title":"Visualizing Genomic Data Using Gviz and Bioconductor","volume":"1418","author":"Hahne","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1038\/nprot.2009.97","article-title":"Mapping identifiers for the integration of genomic datasets with the R\/Bioconductor package biomaRt","volume":"4","author":"Durinck","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"W296","DOI":"10.1093\/nar\/gky427","article-title":"SWISS-MODEL: Homology modelling of protein structures and complexes","volume":"46","author":"Waterhouse","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S162","DOI":"10.1002\/elps.200900140","article-title":"Automated comparative protein structure modeling with SWISS-MODEL and Swiss-PdbViewer: A historical perspective","volume":"30","author":"Guex","year":"2009","journal-title":"Electrophoresis"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.puhe.2021.12.007","article-title":"Long-term trends in the incidence of congenital anomalies in Central China from 1997 to 2019","volume":"203","author":"Yu","year":"2022","journal-title":"Public Health"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1038\/s41893-019-0387-y","article-title":"Air pollution-induced missed abortion risk for pregnancies","volume":"2","author":"Zhang","year":"2019","journal-title":"Nat. Sustain."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1159\/000334260","article-title":"The 22q13.3 Deletion Syndrome (Phelan-McDermid Syndrome)","volume":"2","author":"Phelan","year":"2012","journal-title":"Mol. Syndr."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Bonaglia, M.C., Giorda, R., Beri, S., De Agostini, C., Novara, F., Fichera, M., Grillo, L., Galesi, O., Vetro, A., and Ciccone, R. (2011). Molecular mechanisms generating and stabilizing terminal 22q13 deletions in 44 subjects with Phelan\/McDermid syndrome. PLoS Genet., 7.","DOI":"10.1371\/journal.pgen.1002173"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1038\/ejhg.2008.107","article-title":"Interstitial 22q13 deletions: Genes other than SHANK3 have major effects on cognitive and language development","volume":"16","author":"Wilson","year":"2008","journal-title":"Eur. J. Hum. Genet. EJHG"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1002\/ajmg.a.36513","article-title":"Interstitial 22q13 deletions not involving SHANK3 gene: A new contiguous gene syndrome","volume":"164","author":"Disciglio","year":"2014","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1097\/YPG.0000000000000151","article-title":"Clinical and molecular characterization of three genomic rearrangements at chromosome 22q13.3 associated with autism spectrum disorder","volume":"27","author":"Chen","year":"2017","journal-title":"Psychiatr. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"47","DOI":"10.3233\/PGE-2012-009","article-title":"Interstitial duplication of 22q13.2 in a girl with short stature, impaired speech and language, and dysmorphism","volume":"1","author":"Samanich","year":"2012","journal-title":"J. Pediatr. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1111\/cge.14781","article-title":"Six New Cases of 22q13.2 Gain Including TFC20: First Report of Triplication and Smallest Duplication Associated With Neurodevelopmental Delays","volume":"108","author":"Bizot","year":"2025","journal-title":"Clin. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1186\/s13023-020-01592-5","article-title":"A 29 Mainland Chinese cohort of patients with Phelan-McDermid syndrome: Genotype-phenotype correlations and the role of SHANK3 haploinsufficiency in the important phenotypes","volume":"15","author":"Xu","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13229-018-0205-9","article-title":"Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations","volume":"9","author":"Siper","year":"2018","journal-title":"Mol. Autism"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"McCoy, M.D., Sarasua, S.M., DeLuca, J.M., Davis, S., Phelan, K., Rogers, R.C., and Boccuto, L. (2022). State of the Science for Kidney Disorders in Phelan-McDermid Syndrome: UPK3A, FBLN1, WNT7B, and CELSR1 as Candidate Genes. Genes, 13.","DOI":"10.3390\/genes13061042"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"eaaz3267","DOI":"10.1126\/scitranslmed.aaz3267","article-title":"Autism-associated SHANK3 mutations impair maturation of neuromuscular junctions and striated muscles","volume":"12","author":"Lutz","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1002\/ajmg.a.63312","article-title":"Updated consensus guidelines on the management of Phelan-McDermid syndrome","volume":"191","author":"Srivastava","year":"2023","journal-title":"Am. J. Med. Genet. Part A"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/18\/7130\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:53:29Z","timestamp":1789390409000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/18\/7130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,14]]},"references-count":38,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["jcm15187130"],"URL":"https:\/\/doi.org\/10.3390\/jcm15187130","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,14]]}}}