{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T09:21:36Z","timestamp":1787908896891,"version":"build-2784847793"},"reference-count":21,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Biallelic variants in\n                    <jats:italic>NSMCE2 (MMS21),<\/jats:italic>\n                    which encodes the SUMO E3 ligase subunit of the SMC5\/6 chromatin\u2010maintenance complex, have recently been implicated in microcephalic primordial dwarfism (MPD), corresponding to Seckel syndrome type 10 (OMIM #617246). The SMC5\/6 complex plays essential roles in genome stability, DNA repair, and replication\u2010fork recovery. To date, only two individuals with\n                    <jats:italic>NSMCE2<\/jats:italic>\n                    \u2010related MPD have been reported. Here, we describe an 11\u2010year\u2010old male with compound heterozygous\n                    <jats:italic>NSMCE2<\/jats:italic>\n                    variants (c.346del; c.697_700dupAGGG) and a phenotype consistent with MPD, including severe pre\u2010 and postnatal growth restriction, marked microcephaly, feeding difficulties, characteristic dysmorphic features, dental anomalies, severe insulin resistance with hypertriglyceridemia and hepatic steatosis, primary gonadal failure, renal lithiasis, and skeletal anomalies, including platyspondyly and right\u2010hip osteochondritis. Neuroimaging revealed bifrontal gyral simplification and a cavernous carotid aneurysm. In addition, the proband exhibited a bilateral developmental maculopathy, an ocular feature not previously associated with\n                    <jats:italic>NSMCE2<\/jats:italic>\n                    deficiency. This finding may broaden the phenotypic spectrum associated with\n                    <jats:italic>NSMCE2<\/jats:italic>\n                    \u2010related MPD and highlights the importance of considering\n                    <jats:italic>NSMCE2<\/jats:italic>\n                    in the genetic evaluation of individuals with severe primordial dwarfism presenting with atypical or unexplained retinal findings.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70286","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T04:15:00Z","timestamp":1787890500000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Rare Form of Microcephalic Primordial Dwarfism due to\n                    <scp>\n                      <i>NSMCE2<\/i>\n                    <\/scp>\n                    Deficiency (Seckel Syndrome Type 10): A Report of Macular Involvement"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4054-3651","authenticated-orcid":false,"given":"Cristina","family":"Peduto","sequence":"first","affiliation":[{"name":"Reference Center for Skeletal Dysplasia AP\u2010HP, H\u00f4pital Universitaire Necker\u2010Enfants Malades  Paris France"},{"name":"Department of Clinical Genetics, AP\u2010HP H\u00f4pital Bic\u00eatre, Universit\u00e9 Paris\u2010Saclay  Le Kremlin\u2010Bic\u00eatre France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Huber","sequence":"additional","affiliation":[{"name":"Physiopathological Bases of Skeletal Dysplasia INSERM UMR1163, Institut IMAGINE, Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9ment","family":"Paya","sequence":"additional","affiliation":[{"name":"Cabinet Priv\u00e9 d\u2019Ophtalmologie, Palais Gallien  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Audo","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, CNRS, Institut de la Vision  Paris France"},{"name":"CHNO des Quinze\u2010Vingts Centre de R\u00e9f\u00e9rence Maladies Rares REFERET and INSERM\u2010DGOS CIC1423  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Boddaert","sequence":"additional","affiliation":[{"name":"Pediatric Radiology Department Necker University Hospital, APHP, University of Paris\u2010Cit\u00e9  Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9, Institut Imagine INSERM U1163, F\u201075015  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Cormier\u2010Daire","sequence":"additional","affiliation":[{"name":"Reference Center for Skeletal Dysplasia AP\u2010HP, H\u00f4pital Universitaire Necker\u2010Enfants Malades  Paris France"},{"name":"Physiopathological Bases of Skeletal Dysplasia INSERM UMR1163, Institut IMAGINE, Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12887\u2010019\u20101685\u20102"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes9010036"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/bcr\u20102016\u2010215502"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.955102"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/db10\u20101334"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/15216540310001639661"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.07.048"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.169037"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320120104"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2018.02.002"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/neurintsurg\u20102020\u2010016069"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1129"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI73264"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e04\u201005\u20100436"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2012.12.010"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007942"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00381\u2010010\u20101142\u2010x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.563"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0500537102"}],"container-title":["American 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