{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T05:18:47Z","timestamp":1787721527787,"version":"build-2784847793"},"reference-count":30,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key R&D Program","award":["2024C03151"],"award-info":[{"award-number":["2024C03151"]}]},{"name":"National Key Research and Development Program of China","award":["2022YFC270340"],"award-info":[{"award-number":["2022YFC270340"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Silver\u2013Russell syndrome (SRS) is most commonly caused by epigenetic alterations at 11p15.5 or maternal uniparental disomy of chromosome 7 [upd(7)mat], though other molecular mechanisms remain unclear. While microdeletions encompassing MEST have been associated with SRS-like phenotypes, no pathogenic intragenic MEST variants have been reported to date. We describe a 6-month-old male infant with clinical features suggestive of a SRS-like phenotype, including intrauterine and postnatal growth restriction, triangular facies, prominent forehead, and small extremities. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) revealed neither methylation abnormalities at 11p15.5, 7p13, or 7q32 nor copy number variations (CNVs) in these regions. Trio whole-exome sequencing (trio-WES) identified a paternally inherited splice-site variant (c.890 + 1G &gt; A) in MEST. Given the paternal-specific expression of MEST, this variant resides on the functionally active allele. Based on in silico predictions and clinical correlation, this case identifies MEST as a plausible candidate gene for SRS and provides a rationale for further functional studies. Phenotypic variation exists across molecular subtypes, yet definitive genotype\u2013phenotype correlations await larger, systematically ascertained cohorts.<\/jats:p>","DOI":"10.3390\/genes17090992","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T17:20:28Z","timestamp":1787592028000},"page":"992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Candidate MEST Splice-Site Variant in a Patient with Silver\u2013Russell Syndrome-like Phenotype: First Report and Literature Review"],"prefix":"10.3390","volume":"17","author":[{"given":"Xiaocha","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Genetics and Metabolism, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents\u2019 Health and Disease, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongrong","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Genetics and Metabolism, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents\u2019 Health and Disease, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Genetics and Metabolism, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents\u2019 Health and Disease, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Genetics and Metabolism, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents\u2019 Health and Disease, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixia","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Genetics and Metabolism, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents\u2019 Health and Disease, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kexin","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Genetics and Metabolism, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents\u2019 Health and Disease, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingwen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Genetics and Metabolism, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents\u2019 Health and Disease, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Genetics and Metabolism, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents\u2019 Health and Disease, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Pediatric Healthcare Department, Jiaxing Maternity and Child Health Care Hospital, Jiaxing 314000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4267-9579","authenticated-orcid":false,"given":"Xin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Genetics and Metabolism, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents\u2019 Health and Disease, Hangzhou 310051, China"},{"name":"Zhejiang Key Laboratory of Neonatal Diseases, Hangzhou 310052, China"},{"name":"Binjiang Institute of Zhejiang University, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.placenta.2004.12.003","article-title":"Imprinting of PEG1\/MEST isoform 2 in human placenta","volume":"27","author":"McMinn","year":"2006","journal-title":"Placenta"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/2464","article-title":"Abnormal maternal behaviour and growth restriction associated with loss of the imprinted gene Mest","volume":"20","author":"Lefebvre","year":"1998","journal-title":"Nat. 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