{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:32:38Z","timestamp":1790195558546,"version":"4.1.0"},"reference-count":22,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,13]],"date-time":"2021-11-13T00:00:00Z","timestamp":1636761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST-110-2314-B-195-010-MY3"],"award-info":[{"award-number":["MOST-110-2314-B-195-010-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background: Silver\u2013Russell syndrome (SRS) is a clinically and genetically heterogeneous disorder characterized by severe intrauterine growth retardation, poor postnatal growth, characteristic facial features, and body asymmetry. Hypomethylation of the imprinted genes of the chromosome 11p15.5 imprinting gene cluster and maternal uniparental disomy of chromosome 7 (mUPD7) are the major epigenetic disturbances. The aim of this study was to characterize the epigenotype, genotype, and phenotype of these patients in Taiwan. Methods: Two hundred and six subjects with clinically suspected SRS were referred for diagnostic testing, which was performed by profiling the methylation of H19-associated imprinting center (IC) 1 and the imprinted PEG1\/MEST region using methylation-specific multiplex ligation-dependent probe amplification and high-resolution melting analysis with a methylation-specific polymerase chain reaction assay. We also applied a whole genome strategy to detect copy number changes and loss of heterozygosity. Clinical manifestations were recorded and analyzed according to the SRS scoring system proposed by Bartholdi et al. Results: Among the 206 referred subjects, 100 were classified as having a clinical diagnosis of SRS (score \u2265 8, maximum = 15) and 106 had an SRS score \u2264 7. Molecular lesions were detected in 45% (45\/100) of the subjects with a clinical diagnosis of SRS, compared to 5% (5\/106) of those with an SRS score \u2264 7. Thirty-seven subjects had IC1 hypomethylation, ten subjects had mUPD7, and three subjects had microdeletions. Several clinical features were found to be statistically different (p &lt; 0.05) between the \u201cIC1 hypomethylation\u201d and \u201cmUPD7\u201d groups, including relative macrocephaly at birth (89% vs. 50%), triangular shaped face (89% vs. 50%), clinodactyly of the fifth finger (68% vs. 20%), and SRS score (11.4 \u00b1 2.2 vs. 8.3 \u00b1 2.5). Conclusions: The SRS score was positively correlated with the molecular diagnosis rate (p &lt; 0.001). The SRS subjects with mUPD7 seemed to have fewer typical features and lower SRS scores than those with IC1 hypomethylation. Careful clinical observation and timely molecular confirmation are important to allow for an early diagnosis and multidisciplinary management of these patients.<\/jats:p>","DOI":"10.3390\/jpm11111197","type":"journal-article","created":{"date-parts":[[2021,11,14]],"date-time":"2021-11-14T20:51:53Z","timestamp":1636923113000},"page":"1197","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Epigenotype, Genotype, and Phenotype Analysis of Taiwanese Patients with Silver\u2013Russell Syndrome"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9619-0990","authenticated-orcid":false,"given":"Hsiang-Yu","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Medicine, MacKay Medical College, New Taipei City 25245, Taiwan"},{"name":"Department of Pediatrics, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Department of Medical Research, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"MacKay Junior College of Medicine, Nursing and Management, Taipei 10449, Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan"},{"name":"Department of Rare Disease Center, MacKay Memorial Hospital, Taipei 10449, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Lin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine, MacKay Medical College, New Taipei City 25245, Taiwan"},{"name":"Department of Pediatrics, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"MacKay Junior College of Medicine, Nursing and Management, Taipei 10449, Taiwan"},{"name":"Department of Rare Disease Center, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan"},{"name":"Institute of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sisca","family":"Fran","sequence":"additional","affiliation":[{"name":"Department of Medical Research, MacKay Memorial Hospital, Taipei 10449, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru-Yi","family":"Tu","sequence":"additional","affiliation":[{"name":"Department of Medical Research, MacKay Memorial Hospital, Taipei 10449, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Hui","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Department of Rare Disease Center, MacKay Memorial Hospital, Taipei 10449, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dau-Ming","family":"Niu","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan"},{"name":"Institute of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei 11221, Taiwan"},{"name":"Department of Pediatrics, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Ying","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, MacKay Memorial Hospital, Hsinchu 300, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pao-Chin","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung 800, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Yin","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Pin","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kaohsiung Medical University Chung Ho Memorial Hospital, Kaohsiung 807, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1057-3315","authenticated-orcid":false,"given":"Meng-Che","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Chyn","family":"Chao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Changhua Christian Children\u2019s Hospital, Changhua 500, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Ping","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan"},{"name":"Department of Medicine, Tzu Chi University, Hualian 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5739-5216","authenticated-orcid":false,"given":"Chia-Feng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pen-Hua","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Chung Shan Medical University, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5469-0364","authenticated-orcid":false,"given":"Yu-Wen","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Hao","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, E-DA Hospital, I-Shou University, Kaohsiung 824, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu-Hung","family":"Chu","sequence":"additional","affiliation":[{"name":"Children Growth & Development Department, IHMED International Medical, Taipei 108, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9776-2092","authenticated-orcid":false,"given":"Chih-Kuang","family":"Chuang","sequence":"additional","affiliation":[{"name":"Department of Medical Research, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"College of Medicine, Fu-Jen Catholic University, Taipei 24205, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuan-Pei","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medicine, MacKay Medical College, New Taipei City 25245, Taiwan"},{"name":"Department of Pediatrics, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Department of Medical Research, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Department of Rare Disease Center, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Department of Infant and Child Care, National Taipei University of Nursing and Health Sciences, Taipei 11219, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1542\/peds.12.4.368","article-title":"Syndrome of congenital hemihypertrophy, shortness of stature, and elevated urinary 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Epigenet."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/11\/11\/1197\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:29:43Z","timestamp":1760167783000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/11\/11\/1197"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,13]]},"references-count":22,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["jpm11111197"],"URL":"https:\/\/doi.org\/10.3390\/jpm11111197","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,13]]}}}