{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T18:23:00Z","timestamp":1768414980716,"version":"3.49.0"},"reference-count":30,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T00:00:00Z","timestamp":1628121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Lissencephaly describes a group of conditions characterized by the absence of normal cerebral convolutions and abnormalities of cortical development. To date, at least 20 genes have been identified as involved in the pathogenesis of this condition. Variants in CEP85L, encoding a protein involved in the regulation of neuronal migration, have been recently described as causative of lissencephaly with a posterior-prevalent involvement of the cerebral cortex and an autosomal dominant pattern of inheritance. Here, we describe a 3-year-old boy with slightly delayed psychomotor development and mild dysmorphic features, including bitemporal narrowing, protruding ears with up-lifted lobes and posterior plagiocephaly. Brain MRI at birth identified type 1 lissencephaly, prevalently in the temporo\u2013occipito\u2013parietal regions of both hemispheres with \u201cdouble-cortex\u201d (Dobyns\u2019 1\u20132 degree) periventricular band alterations. Whole-exome sequencing revealed a previously unreported de novo pathogenic variant in the CEP85L gene (NM_001042475.3:c.232+1del). Only 20 patients have been reported as carriers of pathogenic CEP85L variants to date. They show lissencephaly with prevalent posterior involvement, variable cognitive deficits and epilepsy. The present case report indicates the clinical variability associated with CEP85L variants that are not invariantly associated with severe phenotypes and poor outcome, and underscores the importance of including this gene in diagnostic panels for lissencephaly.<\/jats:p>","DOI":"10.3390\/genes12081208","type":"journal-article","created":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T09:35:32Z","timestamp":1628156132000},"page":"1208","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Posterior Lissencephaly Associated with Subcortical Band Heterotopia Due to a Variation in the CEP85L Gene: A Case Report and Refining of the Phenotypic Spectrum"],"prefix":"10.3390","volume":"12","author":[{"given":"Gianluca","family":"Contr\u00f2","sequence":"first","affiliation":[{"name":"Medical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Micalizzi","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Giangiobbe","sequence":"additional","affiliation":[{"name":"Clinical Genomics, Medical Genetics Service, San Raffaele Hospital, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5033-7854","authenticated-orcid":false,"given":"Stefano Giuseppe","family":"Caraffi","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Zuntini","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simonetta","family":"Rosato","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9865-0751","authenticated-orcid":false,"given":"Marzia","family":"Pollazzon","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Terracciano","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Napoli","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanna","family":"Rizzi","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatry Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grazia Gabriella","family":"Salerno","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatry Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1993-8018","authenticated-orcid":false,"given":"Francesca Clementina","family":"Radio","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcello","family":"Niceta","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Parrini","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, Meyer Children\u2019s Hospital, University of Florence, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Fusco","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatry Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giancarlo","family":"Gargano","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renzo","family":"Guerrini","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, Meyer Children\u2019s Hospital, University of Florence, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7736-9672","authenticated-orcid":false,"given":"Marco","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9037-4297","authenticated-orcid":false,"given":"Antonio","family":"Novelli","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orsetta","family":"Zuffardi","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics, Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Livia","family":"Garavelli","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/S1474-4422(14)70040-7","article-title":"Malformations of cortical development: Clinical features and genetic causes","volume":"13","author":"Guerrini","year":"2014","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1159\/000448639","article-title":"Genetic basis of brain malformations","volume":"7","author":"Parrini","year":"2016","journal-title":"Mol. Syndr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1093\/hmg\/ddg086","article-title":"Lissencephaly and the molecular basis of neuronal migration","volume":"1","author":"Kato","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/s41582-020-0395-6","article-title":"International consensus recommendations on the diagnostic work-up for malformations of cortical development","volume":"16","author":"Oegema","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1002\/ajmg.a.38245","article-title":"Lissencephaly: Expanded imaging and clinical classification","volume":"173","author":"Chiari","year":"2017","journal-title":"Am. J. Med. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1093\/brain\/aws019","article-title":"A developmental and genetic classification for malformations of cortical development: Update 2012","volume":"135","author":"Barkovich","year":"2012","journal-title":"Brain"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1086\/374320","article-title":"Refifinement of a 400-kb critical region allows genotypic differentiation between isolated lissencephaly, Miller-Dieker syndrome, and other phenotypes secondary to deletions of 17p13.3","volume":"72","author":"Cardoso","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1038\/gim.2018.8","article-title":"Analysis of 17 genes detects mutations in 81% of 811 patients with lissencephaly","volume":"20","author":"Timms","year":"2018","journal-title":"Genet. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.neuron.2020.01.030","article-title":"Posterior Neocortex-Specific Regulation of Neuronal Migration by CEP85L Identifies Maternal Centriole-Dependent Activation of CDK5","volume":"106","author":"Kodani","year":"2020","journal-title":"Neuron"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.neuron.2020.01.027","article-title":"Pathogenic variants in CEP85L cause sporadic and familial posterior predominant lissencephaly","volume":"106","author":"Tsai","year":"2020","journal-title":"Neuron"},{"key":"ref_11","unstructured":"(2021, January 06). dbSNP, Available online: http:\/\/www.ncbi.nlm.nih.gov\/projects\/SNP."},{"key":"ref_12","unstructured":"1000 Genomes (2020, August 14). A Deep Catalog of Human Genetic Variation. Available online: http:\/\/www.internationalgenome.org\/."},{"key":"ref_13","unstructured":"Exome Variant Server (2020, July 03). Available online: http:\/\/evs.gs.washington.edu\/EVS\/."},{"key":"ref_14","unstructured":"ExAc (2020, July 03). Available online: gs:\/\/gnomad-public\/legacy."},{"key":"ref_15","unstructured":"GnomAD (2020, July 03). Available online: http:\/\/gnomad.broadinstitute.org\/."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kopanos, C., Tsiolkas, V., Kouris, A., Chapple, C.E., Albarca Aguilera, M., Meyer, R., and Massouras, A. (2018). VarSome: The Human Genomic Variant Search Engine. Bioinformatics, 35.","DOI":"10.1101\/367359"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"ACMG Laboratory Quality Assurance Committee Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.ajhg.2018.09.001","article-title":"Mutations in KCNK4 that Affect Gating Cause a Recognizable Neurodevelopmental Syndrome","volume":"103","author":"Bauer","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.ajhg.2019.07.007","article-title":"Aberrant Function of the C-Terminal Tail of HIST1H1E Accelerates Cellular Senescence and Causes Premature Aging","volume":"105","author":"Flex","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.ajhg.2021.01.015","article-title":"SPEN haploinsufficiency causes a neurodevelopmental disorder overlapping proximal 1p36 deletion syndrome with an episignature of X chromosomes in females","volume":"108","author":"Radio","year":"2021","journal-title":"Am. J. Hum. Genet."},{"key":"ref_21","unstructured":"Li, H. (2013). Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. arXiv."},{"key":"ref_22","first-page":"11.10.1","article-title":"From FastQ Data to High-Confidence Variant Calls: The Genome Analysis Toolkit Best Practices Pipeline","volume":"43","author":"Carneiro","year":"2013","journal-title":"Curr. Protoc. Bioinform."},{"key":"ref_23","unstructured":"(2021, May 24). Human Splicing Finder. Available online: http:\/\/www.umd.be\/HSF\/."},{"key":"ref_24","unstructured":"(2021, May 24). Berkeley Drosophila Genome Project\u2014Splice Site Prediction by Neural Network. Available online: https:\/\/www.fruitfly.org\/seq_tools\/splice.html."},{"key":"ref_25","unstructured":"(2021, May 24). NetGene2. Available online: http:\/\/www.cbs.dtu.dk\/services\/NetGene2\/."},{"key":"ref_26","unstructured":"(2021, May 24). MaxEntScan. Available online: http:\/\/hollywood.mit.edu\/burgelab\/maxent\/Xmaxentscan_scoreseq.html."},{"key":"ref_27","unstructured":"(2020, January 06). SPiCEv2.1.5. Available online: https:\/\/sourceforge.net\/projects\/spicev2-1\/."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1212\/WNL.61.8.1042","article-title":"Mosaic mutations of the LIS1 gene cause subcortical band heterotopia","volume":"61","author":"Sicca","year":"2003","journal-title":"Neurology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/jhg.2011.128","article-title":"Exome sequencing can detect pathogenic mosaic mutations present at low allele frequencies","volume":"57","author":"Pagnamenta","year":"2012","journal-title":"J. Hum. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3290","DOI":"10.1242\/jcs.180463","article-title":"Characterization of Cep85\u2014A new antagonist of Nek2A that is involved in the regulation of centrosome disjunction","volume":"128","author":"Chen","year":"2015","journal-title":"J. Cell Sci."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/8\/1208\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:40:55Z","timestamp":1760164855000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/8\/1208"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,5]]},"references-count":30,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["genes12081208"],"URL":"https:\/\/doi.org\/10.3390\/genes12081208","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,5]]}}}