{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T01:57:11Z","timestamp":1790042231725,"version":"4.0.1"},"reference-count":14,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,4,29]],"date-time":"2016-04-29T00:00:00Z","timestamp":1461888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Telethon, Italy","award":["TGM11Z06"],"award-info":[{"award-number":["TGM11Z06"]}]},{"name":"Telethon-UILDM (Unione Italiana Lotta alla Distrofia Muscolare)","award":["GUP11006"],"award-info":[{"award-number":["GUP11006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:p>Primary autosomal recessive microcephaly (<jats:styled-content style=\"fixed-case\">MCPH<\/jats:styled-content>) is a developmental disorder characterized by prenatal onset of abnormal brain growth. <jats:styled-content style=\"fixed-case\">MCPH<\/jats:styled-content> occurs both alone and as part of a broad range of neurodevelopmental syndromes with or without cortical malformations and growth retardation. Here we report a consanguineous Moroccan family with two siblings affected by severe primary microcephaly, failure to thrive, congenital dermatitis and severe developmental delay. Brain magnetic resonance imaging showed lissencephaly of frontal lobes and periventricular heterotopia of the gray matter. We performed both Comparative Genomic Hybridization array and whole exome sequencing (<jats:styled-content style=\"fixed-case\">WES<\/jats:styled-content>) analyses of the kindred. No quantitative defects were detected. However, <jats:styled-content style=\"fixed-case\">WES<\/jats:styled-content> identified a new homozygous missense variation in the penultimate nucleotide of exon 23 of <jats:italic><jats:styled-content style=\"fixed-case\">RTTN<\/jats:styled-content><\/jats:italic> gene (c.<jats:styled-content style=\"fixed-case\">2953A<\/jats:styled-content>&gt;G;<jats:styled-content style=\"fixed-case\">pArg985Gly<\/jats:styled-content>). <jats:styled-content style=\"fixed-case\">cDNA<\/jats:styled-content> sequencing revealed two abnormal spliced products, one lacking only exon 23 and the other lacking exons 22 and 23 (out\u2010of\u2010frame). <jats:styled-content style=\"fixed-case\">RTTN<\/jats:styled-content> is a protein involved in cilia structure and function. Homozygous mutations in <jats:italic><jats:styled-content style=\"fixed-case\">RTTN<\/jats:styled-content><\/jats:italic> gene have been described in bilateral diffuse isolated polymicrogyria and, more recently, in microcephalic primordial dwarfism (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>). We found a novel homozygous mutation in <jats:italic><jats:styled-content style=\"fixed-case\">RTTN<\/jats:styled-content><\/jats:italic> associated with microcephalic <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> as well as complex brain malformations and congenital dermatitis, thus expanding the phenotypic spectrum of both <jats:italic><jats:styled-content style=\"fixed-case\">RTTN<\/jats:styled-content><\/jats:italic>\u2010associated diseases and ciliary dysfunction.<\/jats:p>","DOI":"10.1111\/cge.12771","type":"journal-article","created":{"date-parts":[[2016,3,5]],"date-time":"2016-03-05T16:46:51Z","timestamp":1457196411000},"page":"445-450","source":"Crossref","is-referenced-by-count":27,"title":["Expanding the phenotype of <i><scp>RTTN<\/scp><\/i> variations: a new family with primary microcephaly, severe growth failure, brain malformations and dermatitis"],"prefix":"10.1111","volume":"90","author":[{"given":"A.","family":"Grandone","sequence":"first","affiliation":[{"name":"Dipartimento della Donna, del Bambino, di Chirurgia Generale e Specialistica Seconda Universit\u00e0 degli Studi di Napoli  Naples  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Torella","sequence":"additional","affiliation":[{"name":"Dipartimento di Biochimica, Biofisica e Patologia Generale Seconda Universit\u00e0 degli Studi di Napoli  Naples Italy"},{"name":"Telethon Institute of Genetics and Medicine (TIGEM)  Pozzuoli (NA)  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Santoro","sequence":"additional","affiliation":[{"name":"Dipartimento della Donna, del Bambino, di Chirurgia Generale e Specialistica Seconda Universit\u00e0 degli Studi di Napoli  Naples  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Giugliano","sequence":"additional","affiliation":[{"name":"Dipartimento di Biochimica, Biofisica e Patologia Generale Seconda Universit\u00e0 degli Studi di Napoli  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"del Vecchio Blanco","sequence":"additional","affiliation":[{"name":"Dipartimento di Biochimica, Biofisica e Patologia Generale Seconda Universit\u00e0 degli Studi di Napoli  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Mutarelli","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM)  Pozzuoli (NA)  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Cirillo","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento Seconda Universit\u00e0 degli Studi di Napoli  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Cirillo","sequence":"additional","affiliation":[{"name":"Dipartimento della Donna, del Bambino, di Chirurgia Generale e Specialistica Seconda Universit\u00e0 degli Studi di Napoli  Naples  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Piluso","sequence":"additional","affiliation":[{"name":"Dipartimento di Biochimica, Biofisica e Patologia Generale Seconda Universit\u00e0 degli Studi di Napoli  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Capristo","sequence":"additional","affiliation":[{"name":"Dipartimento della Donna, del Bambino, di Chirurgia Generale e Specialistica Seconda Universit\u00e0 degli Studi di Napoli  Naples  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Festa","sequence":"additional","affiliation":[{"name":"Dipartimento della Donna, del Bambino, di Chirurgia Generale e Specialistica Seconda Universit\u00e0 degli Studi di Napoli  Naples  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Marzuillo","sequence":"additional","affiliation":[{"name":"Dipartimento della Donna, del Bambino, di Chirurgia Generale e Specialistica Seconda Universit\u00e0 degli Studi di Napoli  Naples  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Miraglia del Giudice","sequence":"additional","affiliation":[{"name":"Dipartimento della Donna, del Bambino, di Chirurgia Generale e Specialistica Seconda Universit\u00e0 degli Studi di Napoli  Naples  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Perrone","sequence":"additional","affiliation":[{"name":"Dipartimento della Donna, del Bambino, di Chirurgia Generale e Specialistica Seconda Universit\u00e0 degli Studi di Napoli  Naples  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Nigro","sequence":"additional","affiliation":[{"name":"Dipartimento di Biochimica, Biofisica e Patologia Generale Seconda Universit\u00e0 degli Studi di Napoli  Naples Italy"},{"name":"Telethon Institute of Genetics and Medicine (TIGEM)  Pozzuoli (NA)  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,4,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2012-302882"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcp.2015.05.015"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-15-S3-S5"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(02)00003-5"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-007-9023-7"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2774"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.07.008"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.10.012"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2014.06.030"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3122"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2014-102790"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.05.025"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv261"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2014.483"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.12771","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.12771","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.12771","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T12:06:31Z","timestamp":1694261191000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.12771"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4,29]]},"references-count":14,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2016,11]]}},"alternative-id":["10.1111\/cge.12771"],"URL":"https:\/\/doi.org\/10.1111\/cge.12771","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,29]]}}}