{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:14:41Z","timestamp":1761718481346},"reference-count":9,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2016,6,8]],"date-time":"2016-06-08T00:00:00Z","timestamp":1465344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:sec><jats:label \/><jats:p>Biallelic defects in the <jats:italic>RIN2<\/jats:italic> gene, encoding the Ras and Rab interactor 2 protein, are associated with a rare autosomal recessive connective tissue disorder, with only nine patients from four independent families reported to date. The condition was initially termed MACS syndrome (macrocephaly, alopecia, cutis laxa, and scoliosis), based on the clinical features of the first identified family; however, with the expansion of the clinical phenotype in additional families, it was subsequently coined RIN2 syndrome. Hallmark features of this condition include dysmorphic facial features with striking, progressive facial coarsening, sparse hair, normal to enlarged occipitofrontal circumference, soft redundant and\/or hyperextensible skin, and scoliosis. Patients with RIN2 syndrome present phenotypic overlap with other conditions, including EDS (especially the dermatosparaxis and kyphoscoliosis subtypes). Here, we describe a 10th patient, the first patient of Caucasian origin and the oldest reported patient so far, who harbors the previously identified homozygous <jats:italic>RIN2<\/jats:italic> mutation c.1878dupC (p. (Ile627Hisfs*7)). Besides the hallmark features, this patient also presents problems not previously associated with RIN2 syndrome, including cervical vertebral fusion, mild hearing loss, and colonic fibrosis. We provide an overview of the clinical findings in all reported patients with <jats:italic>RIN2<\/jats:italic> mutations and summarize some of the possible pathogenic mechanisms that may underlie this condition. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37789","type":"journal-article","created":{"date-parts":[[2016,6,9]],"date-time":"2016-06-09T05:00:10Z","timestamp":1465448410000},"page":"2408-2415","source":"Crossref","is-referenced-by-count":9,"title":["RIN2 syndrome: Expanding the clinical phenotype"],"prefix":"10.1002","volume":"170","author":[{"given":"Simonetta","family":"Rosato","sequence":"first","affiliation":[{"name":"Clinical Genetics Unit Department of Obstetrics and Pediatrics, Arcispedale Santa Maria Nuova\u2010IRCCS Reggio Emilia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Delfien","family":"Syx","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Ghent University and Ghent University Hospital Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Ivanovski","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit Department of Obstetrics and Pediatrics, Arcispedale Santa Maria Nuova\u2010IRCCS Reggio Emilia Italy"},{"name":"Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant Oncology and Regenerative Medicine, University of Modena and Reggio Emilia Modena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marzia","family":"Pollazzon","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit Department of Obstetrics and Pediatrics, Arcispedale Santa Maria Nuova\u2010IRCCS Reggio Emilia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Santodirocco","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit Department of Obstetrics and Pediatrics, Arcispedale Santa Maria Nuova\u2010IRCCS Reggio Emilia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loredana","family":"De Marco","sequence":"additional","affiliation":[{"name":"Anatomic Pathology Unit Arcispedale Santa Maria Nuova\u2010IRCCS Reggio Emilia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Beltrami","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Arcispedale Santa Maria Nuova\u2010IRCCS Reggio Emilia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bert","family":"Callewaert","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Ghent University and Ghent University Hospital Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Livia","family":"Garavelli","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit Department of Obstetrics and Pediatrics, Arcispedale Santa Maria Nuova\u2010IRCCS Reggio Emilia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fransiska","family":"Malfait","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Ghent University and Ghent University Hospital Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,6,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33712"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36277"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.07.001"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2012.118"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M510531200"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M106276200"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2012.110"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-010-0829-0"},{"key":"e_1_2_7_10_1","unstructured":"VerloesA BenmansourA MortierG PierardG Le MerrerM.2005. A new recessive connective tissue disorder with fleshy swelling of lips lid and cheeks macrocephaly hyperextensible skin and severe scoliosis. 55th annual meeting of the American Society of Human Genetics. Salt Lake City."}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.37789","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.37789","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.37789","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T23:39:34Z","timestamp":1696635574000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.37789"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,8]]},"references-count":9,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2016,9]]}},"alternative-id":["10.1002\/ajmg.a.37789"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.37789","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,8]]}}}