{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T23:46:41Z","timestamp":1774136801563,"version":"3.50.1"},"reference-count":16,"publisher":"BMJ","issue":"3","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2023,9,25]]},"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Neurodevelopmental disorders (NDDs) impact both the development and functioning of the brain and exhibit clinical and genetic variability. RAP and RAB proteins, belonging to the RAS superfamily, are identified as established contributors to NDDs. However, the involvement of SGSM (small G protein signalling modulator), another member of the RAS family, in NDDs has not been previously documented.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Proband-only or trio exome sequencing was performed on DNA samples obtained from affected individuals and available family members. The variant prioritisation process focused on identifying rare deleterious variants. International collaboration aided in the identification of additional affected individuals.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified 13 patients from 8 families of Ashkenazi Jewish origin who all carried the same homozygous frameshift variant in <jats:italic>SGSM3<\/jats:italic> gene. The variant was predicted to cause a loss of function, potentially leading to impaired protein structure or function. The variant co-segregated with the disease in all available family members. The affected individuals displayed mild global developmental delay and mild to moderate intellectual disability. Additional prevalent phenotypes observed included hypotonia, behavioural challenges and short stature.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>An Ashkenazi Jewish homozygous founder variant in <jats:italic>SGSM3<\/jats:italic> was discovered in individuals with NDDs and short stature. This finding establishes a connection between another member of the RAS family and NDDs. Additional research is needed to uncover the specific molecular mechanisms by which SGSM3 influences neurodevelopmental processes and the regulation of growth.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg-2023-109504","type":"journal-article","created":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T13:25:34Z","timestamp":1697203534000},"page":"289-293","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Intellectual disability syndrome associated with a homozygous founder variant in <i>SGSM3<\/i> in Ashkenazi Jews"],"prefix":"10.1136","volume":"61","author":[{"given":"Rivka","family":"Birnbaum","sequence":"first","affiliation":[{"name":"Department of Genetics, Hadassah Medical Center, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shlomit","family":"Ezer","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nava Shaul","family":"Lotan","sequence":"additional","affiliation":[{"name":"Department of Genetics, Hadassah Medical Center, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avital","family":"Eilat","sequence":"additional","affiliation":[{"name":"Department of Genetics, Hadassah Medical Center, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keren","family":"Sternlicht","sequence":"additional","affiliation":[{"name":"Genetics Institute, Shamir Medical Center, Tzrifin, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilach","family":"Benyamini","sequence":"additional","affiliation":[{"name":"Genetics Institute, Shamir Medical Center, Tzrifin, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orit","family":"Reish","sequence":"additional","affiliation":[{"name":"Genetics Institute, Shamir Medical Center, Tzrifin, Israel"},{"name":"Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0065-1922","authenticated-orcid":false,"given":"Tzipora","family":"Falik-Zaccai","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Western Galilee Hospital-Nahariya, Nahariya, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gali","family":"Ben-Gad","sequence":"additional","affiliation":[{"name":"Department of Child Development, Galilee Medical Center, Nahariya, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raya","family":"Rod","sequence":"additional","affiliation":[{"name":"The Center for Child Development and Pediatric Neurology, Western Galilee Hospital-Naharyia, Nahariya, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5807-9223","authenticated-orcid":false,"given":"Reeval","family":"Segel","sequence":"additional","affiliation":[{"name":"Genetics, Shaare-Zedek, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Kim","sequence":"additional","affiliation":[{"name":"Genetics, Ann and Robert H Lurie Children's Hospital of Chicago, Chicago, Illinois, USA"},{"name":"Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barabra","family":"Burton","sequence":"additional","affiliation":[{"name":"Ann & Robert H. 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