{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T03:31:57Z","timestamp":1785209517924,"version":"3.55.0"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"5","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:p><jats:italic>POC1A<\/jats:italic> encodes a protein with a role in centriole assembly and stability, and in ciliogenesis. Biallelic loss-of-function mutations affecting <jats:italic>POC1A<\/jats:italic> cause SOFT syndrome, an ultra-rare condition characterized by short stature, onychodysplasia, facial dysmorphism and hypotrichosis. Using exome sequencing, we identified a homozygous frameshift mutation (c.1047_1048dupC; p.G337Rfs*25) in a patient presenting with short stature, facial hirsutism, alopecia, dyslipidemia and extreme insulin resistance. The truncating variant affected exon 10, which is retained in only two of the three <jats:italic>POC1A<\/jats:italic>-mature RNAs, due to alternative processing of the transcript. Clinical discrepancies with SOFT syndrome support the hypothesis that <jats:italic>POC1A<\/jats:italic> mutations affecting exon 10 are associated with a distinct condition, corroborating a previous hypothesis based on a similar case. Furthermore, this report provides an additional example of a genetic condition presenting with clinical heterogeneity due to alternative transcript processing. In conclusion, <jats:italic>POC1A<\/jats:italic> mutations in exon 10 should be taken into account in patients with extreme insulin resistance and short stature.<\/jats:p>","DOI":"10.1530\/eje-17-0431","type":"journal-article","created":{"date-parts":[[2017,8,18]],"date-time":"2017-08-18T00:20:17Z","timestamp":1503015617000},"page":"K21-K27","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":13,"title":["A syndromic extreme insulin resistance caused by biallelic POC1A mutations in exon 10"],"prefix":"10.1093","volume":"177","author":[{"given":"Elisa","family":"Giorgio","sequence":"first","affiliation":[{"name":"1Department of Medical Sciences, University of Torino, Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Rubino","sequence":"additional","affiliation":[{"name":"2Department of Neuroscience \u2018Rita Levi Montalcini\u2019, University of Torino, Torino, Italy"},{"name":"3Koelliker Hospital, Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Bruselles","sequence":"additional","affiliation":[{"name":"4Department of Oncology and Molecular Medicine, Istituto Superiore di Sanit\u00e0, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Pizzi","sequence":"additional","affiliation":[{"name":"5Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Ges\u00f9 IRCSS, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Innocenzo","family":"Rainero","sequence":"additional","affiliation":[{"name":"2Department of Neuroscience \u2018Rita Levi Montalcini\u2019, University of Torino, Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Duca","sequence":"additional","affiliation":[{"name":"3Koelliker Hospital, Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Sirchia","sequence":"additional","affiliation":[{"name":"1Department of Medical Sciences, University of Torino, Torino, Italy"},{"name":"6Medical Genetics Unit, Citt\u00e0 della Salute e della Scienza University Hospital, Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Pasini","sequence":"additional","affiliation":[{"name":"1Department of Medical Sciences, University of Torino, Torino, Italy"},{"name":"6Medical Genetics Unit, Citt\u00e0 della Salute e della Scienza University Hospital, Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"5Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Ges\u00f9 IRCSS, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Brusco","sequence":"additional","affiliation":[{"name":"1Department of Medical Sciences, University of Torino, Torino, Italy"},{"name":"6Medical Genetics Unit, Citt\u00e0 della Salute e della Scienza University Hospital, Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"key":"ref81","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/ng.3282","article-title":"Mutations in KCNH1 and ATP6V1B2 cause Zimmermann-Laband syndrome","volume":"47","year":"2015","journal-title":"Nature Genetics"},{"key":"ref01","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1242\/jcs.111203","article-title":"Poc1A and Poc1B act together in human cells to ensure centriole integrity","volume":"126","year":"2013","journal-title":"Journal of Cell Science"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.ajhg.2012.05.025","article-title":"POC1A truncation mutation causes a ciliopathy in humans characterized by primordial dwarfism","volume":"91","year":"2012","journal-title":"American Journal of Human Genetics"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/ng.2892","article-title":"A general framework for estimating the relative pathogenicity of human genetic variants","volume":"46","year":"2014","journal-title":"Nature Genetics"},{"key":"ref161","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/ng867","article-title":"Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alstrom syndrome","volume":"31","year":"2002","journal-title":"Nature Genetics"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/ng.3035","article-title":"Mutations in ZBTB20 cause Primrose syndrome","volume":"46","year":"2014","journal-title":"Nature Genetics"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/jhg.2015.174","article-title":"SOFT syndrome caused by compound heterozygous mutations of POC1A and its skeletal manifestation","volume":"61","year":"2016","journal-title":"Journal of Human Genetics"},{"key":"ref141","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/nn.3713","article-title":"One gene, many neuropsychiatric disorders: lessons from Mendelian diseases","volume":"17","year":"2014","journal-title":"Nature Neuroscience"},{"key":"ref111","first-page":"201334","article-title":"LiuXJianXBoerwinkleE dbNSFP a database of human non - synonymous SNVs and their functional predictions and annotations","volume":"2","journal-title":"Human Mutation"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1530\/JME-15-0090","article-title":"Truncation of POC1A associated with short stature and extreme insulin resistance","volume":"55","year":"2015","journal-title":"Journal of Molecular Endocrinology"},{"key":"ref171","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1136\/jmg.2009.067298","article-title":"Molecular analysis of pericentrin gene (PCNT) in a series of 24 Seckel\/microcephalic osteodysplastic primordial dwarfism type II (MOPD II) families","volume":"47","year":"2010","journal-title":"Journal of Medical Genetics"},{"key":"ref21","first-page":"210","article-title":"Two novel POC1A mutations in the primordial dwarfism, SOFT syndrome: clinical homogeneity but also unreported malformations","volume":"170A","year":"2016","journal-title":"American Journal of Medical Genetics Part A"},{"key":"ref121","doi-asserted-by":"publisher","first-page":"201240","DOI":"10.1093\/nar\/gks487","article-title":"SeelowDSchuelkeM HomozygosityMapper bridging the gap between homozygosity mapping and deep sequencing","year":"2012","journal-title":"Nucleic Acids Research"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4161\/fly.19695","article-title":"A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3","volume":"6","year":"2012","journal-title":"Fly"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"5378","DOI":"10.1093\/hmg\/ddv261","article-title":"Novel POC1A mutation in primordial dwarfism reveals new insights for centriole biogenesis","volume":"24","year":"2015","journal-title":"Human Molecular Genetics"},{"key":"ref151","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.1093\/hmg\/ddv066","article-title":"Mutation in exon 1a of PLEC, leading to disruption of plectin isoform 1a, causes autosomal-recessive skin-only epidermolysis bullosa simplex","volume":"24","year":"2015","journal-title":"Human Molecular Genetics"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.ajhg.2012.06.003","article-title":"Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis syndrome is caused by a POC1A mutation","volume":"91","year":"2012","journal-title":"American Journal of Human Genetics"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.ajhg.2015.03.001","article-title":"Mutations impairing GSK3-mediated MAF phosphorylation cause cataract, deafness, intellectual disability, seizures, and a down syndrome-like facies","volume":"96","year":"2015","journal-title":"American Journal of Human Genetics"}],"container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/177\/5\/EJE-17-0431.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1530\/EJE-17-0431","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:10:54Z","timestamp":1676391054000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/177\/5\/K21\/6655315"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11]]},"references-count":18,"journal-issue":{"issue":"5"},"URL":"https:\/\/doi.org\/10.1530\/eje-17-0431","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11]]}}}