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Cell Dev. Biol."],"abstract":"<jats:p>Nonsense variants in KIDINS220\/ARMS were identified as the main cause of <jats:underline>s<\/jats:underline>pastic paraplegia, <jats:underline>i<\/jats:underline>ntellectual disability, <jats:underline>n<\/jats:underline>ystagmus, and <jats:underline>o<\/jats:underline>besity (SINO) syndrome, a rare disease with birth defects in brachycephaly, neurological disorder, and obesity. The cause of neural cell dysfunction by KIDINS220\/ARMS were extensively studied while the cause of obesity in SINO syndrome remains elusive. Here, we identified KIDINS220\/ARMS as an adipocyte differentiation-regulating gene. A Chinese family, mother and her two sons, all showed severe symptoms of SINO syndrome. G-banding karyotyping, chromosome microarray analysis, and whole exome sequencing revealed a novel amber mutation, c.3934G&amp;gt;T (p. E1312X), which was close to the C-terminal region of KIDINS220\/ARMS and resulted in the premature of the protein. Both the mRNA and protein levels of KIDINS220\/ARMS gradually decreased during adipocyte differentiation. Knockdown of KINDINS220\/ARMS could prompt adipocyte differentiation and lipid accumulation while overexpression of KIDINS220\/ARMS decrease the rate of matured adipocytes. Furthermore, we demonstrated that KIDINS220\/ARMS inhibits adipocyte maturation through sustained extracellular signal-regulated kinase signaling. In conclusion, this is the first report about a vertical heredity of severe dominant pathogenic mutation of KIDINS220\/ARMS, suggested that KIDINS220\/ARMS played a negative role in adipocyte maturation, explained the cause of obesity in SINO syndrome and could highlight the importance of adipocyte differentiation in neuron functions.<\/jats:p>","DOI":"10.3389\/fcell.2021.619475","type":"journal-article","created":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T06:24:35Z","timestamp":1614839075000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["SINO Syndrome Causative KIDINS220\/ARMS Gene Regulates Adipocyte Differentiation"],"prefix":"10.3389","volume":"9","author":[{"given":"Kaihui","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenxing","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqiang","family":"Lv","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisen","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianyuan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongtao","family":"Gai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shimin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiyuan","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"S498","DOI":"10.1097\/00005768-200009001-00009","article-title":"Compendium of physical activities: an update of activity codes and MET intensities.","volume":"32","author":"Ainsworth","year":"2000","journal-title":"Med. 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