{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:54:03Z","timestamp":1790376843842,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    SUMOylation involves covalent attachment of small ubiquitin\u2010like modifier (SUMO) proteins to specific lysine residues on target proteins and regulates various aspects of their function. Sentrin\u2010specific proteases (SENPs) are key players in both the conjugation reaction of SUMO proteins to their targets and the subsequent deconjugation of SUMO\u2010conjugated substrates. Here, we provide the first comprehensive prenatal description of a lethal syndrome linked to a novel homozygous stop\u2010gain variant in\n                    <jats:italic>SENP7<\/jats:italic>\n                    c.745C&gt;T; p.(Arg249*) in a consanguineous Egyptian family with a history of three fetal deaths, all presenting with multiple congenital anomalies. Similar anomalies were observed through ultrasound assessment of the current fetus, including arthrogryposis multiplex congenita, CNS malformations, congenital heart disease, and renal anomalies. Singleton exome sequencing (ES) of fetal DNA revealed a\n                    <jats:italic>SENP7<\/jats:italic>\n                    variant allele, which results in a premature termination codon, and the mutant mRNA is predicted to be degraded by nonsense\u2010mediated decay (NMD). This leads to impaired gene function, particularly disrupting SENP7's isopeptidase activity in deconjugating polySUMO chains. Our findings broaden the molecular spectrum of\n                    <jats:italic>SENP7<\/jats:italic>\n                    variants and emphasize their essential role in the development of the nervous, musculoskeletal, cardiovascular, and renal systems. This study offers new insights into the genotype\u2013phenotype correlations observed in lethal congenital contracture syndromes and severe embryological abnormalities.\n                  <\/jats:p>","DOI":"10.1111\/cge.14695","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:35:03Z","timestamp":1736210103000},"page":"673-679","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Lethal Phenotype and Expansion of the Clinical Spectrum of Biallelic Loss of Function Variant in\n                    <scp>\n                      <i>SENP7<\/i>\n                    <\/scp>\n                    Gene Unveiled by Whole Exome Sequencing"],"prefix":"10.1111","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7141-5129","authenticated-orcid":false,"given":"Ahmed K.","family":"Saad","sequence":"first","affiliation":[{"name":"Medical Molecular Genetics Department, Human Genetics and Genome Research Institute National Research Centre (NRC)  Cairo Egypt"},{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagwa H.","family":"Hassan","sequence":"additional","affiliation":[{"name":"Zoology Department, Faculty of Science Ain Shams University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala N.","family":"Soliman","sequence":"additional","affiliation":[{"name":"Medical Molecular Genetics Department, Human Genetics and Genome Research Institute National Research Centre (NRC)  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7840-0002","authenticated-orcid":false,"given":"Maha S.","family":"Zaki","sequence":"additional","affiliation":[{"name":"Clinical Genetics Department, Human Genetics and Genome Research Institute National Research Centre (NRC)  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameh M.","family":"Senousy","sequence":"additional","affiliation":[{"name":"Prenatal Diagnosis and Fetal Medicine Department, Human Genetics and Genome Research Institute National Research Centre (NRC)  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7572-9128","authenticated-orcid":false,"given":"Sara H.","family":"El\u2010dessouky","sequence":"additional","affiliation":[{"name":"Prenatal Diagnosis and Fetal Medicine Department, Human Genetics and Genome Research Institute National Research Centre (NRC)  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.190629"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749\u20106632.2010.05819.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.04.011"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2018.4280"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929\u2010024\u201001003\u2010y"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15319"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/CELLS11050814"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20100504"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2013.141"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg\u20102023\u2010109267"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2024.114180"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.53903\/01212095.203"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859\u2010019\u20103169\u20107"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/PD.5717"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2020.09.002"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2016.03.028"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu16010077"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000014168"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2019.08.003"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201005321\u20102"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201073400\u2010w"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2024.107319"}],"container-title":["Clinical 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