{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:36:14Z","timestamp":1787016974703,"version":"build-2736575974"},"reference-count":43,"publisher":"BMJ","issue":"11","funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["(NWO, 724.016.003)."],"award-info":[{"award-number":["(NWO, 724.016.003)."]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2023,6,8]]},"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>SUMOylation involves the attachment of small ubiquitin-like modifier (SUMO) proteins to specific lysine residues on thousands of substrates with target-specific effects on protein function. Sentrin-specific proteases (SENPs) are proteins involved in the maturation and deconjugation of SUMO. Specifically, SENP7 is responsible for processing polySUMO chains on targeted substrates including the heterochromatin protein 1\u03b1 (HP1\u03b1).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed exome sequencing and segregation studies in a family with several infants presenting with an unidentified syndrome. RNA and protein expression studies were performed in fibroblasts available from one subject.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified a kindred with four affected subjects presenting with a spectrum of findings including congenital arthrogryposis, no achievement of developmental milestones, early respiratory failure, neutropenia and recurrent infections. All died within four\u2009months after birth. Exome sequencing identified a homozygous stop gain variant in\n                      <jats:italic>SENP7<\/jats:italic>\n                      c.1474C&gt;T; p.(Gln492*) as the probable aetiology. The proband\u2019s fibroblasts demonstrated decreased mRNA expression. Protein expression studies showed significant protein dysregulation in total cell lysates and in the chromatin fraction. We found that HP1\u03b1 levels as well as different histones and H3K9me3 were reduced in patient fibroblasts. These results support previous studies showing interaction between SENP7 and HP1\u03b1, and suggest loss of SENP7 leads to reduced heterochromatin condensation and subsequent aberrant gene expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results suggest a critical role for SENP7 in nervous system development, haematopoiesis and immune function in humans.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jmg-2023-109267","type":"journal-article","created":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T13:20:46Z","timestamp":1689600046000},"page":"1133-1141","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Exome sequencing links the SUMO protease SENP7 with fatal arthrogryposis multiplex congenita, early respiratory failure and neutropenia"],"prefix":"10.1136","volume":"60","author":[{"given":"Nadra","family":"Samra","sequence":"first","affiliation":[{"name":"Department of Genetics, Ziv Medical Center, Safed, Israel"},{"name":"Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolette S","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilham","family":"Morani","sequence":"additional","affiliation":[{"name":"Department of Genetics, Ziv Medical Center, Safed, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reli Rachel","family":"Kakun","sequence":"additional","affiliation":[{"name":"The Clinical Research Institute, Rambam Health Care Campus, Haifa, 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