{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T21:07:19Z","timestamp":1790024839662,"version":"4.0.1"},"reference-count":19,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T00:00:00Z","timestamp":1690502400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Russian Federation for RCMG"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Here we present a patient with a cranioectodermal phenotype associated with pathogenic variants in the IFT140 gene. Most frequently, pathogenic variants in IFT140 correspond to the phenotype of Mainzer\u2013Saldino syndrome. Only four patients have previously been described with this cranioectodermal phenotype and variants in IFT140. In comparison to other IFT140-cranioectodermal patients, our proband had similar skeletal features among with early onset end-stage renal failure that required kidney transplantation but did not have common ophthalmological features such as retinopathy, optic nerve atrophy, or nystagmus. Following exome sequencing, a splicing variant and exons 27\u201330 tandem duplication were suspected and further validated. The two other patients with Mainzer\u2013Saldino syndrome that we described displayed a typical clinical picture but a special diagnostic journey. In both cases, at first only one pathogenic variant was detected following panel or exome NGS sequencing. Further WGS was performed for one of them where tandem duplication was found. Screening the third patient for the same tandem duplication was successful and revealed the presence of this duplication. Thus, we suggest that the description of the clinical feature polymorphism in a rare IFT140-cranioectodermal phenotype is extremely important for providing genetic counseling for families, as well as the formation of the correct diagnostic path for patients with a variant in IFT140.<\/jats:p>","DOI":"10.3390\/genes14081553","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T01:28:46Z","timestamp":1690766926000},"page":"1553","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Rare IFT140-Associated Phenotype of Cranioectodermal Dysplasia and Features of Diagnostic Journey in Patients with Suspected Ciliopathies"],"prefix":"10.3390","volume":"14","author":[{"given":"Margarita","family":"Sharova","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2672-6294","authenticated-orcid":false,"given":"Tatyana","family":"Markova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Sumina","sequence":"additional","affiliation":[{"name":"State Healthcare Institution of Sverdlovsk Region \u201cClinical and Diagnostic Center \u201cMother\u2019s and Child Health Protection\u201d, 620067 Ekaterinburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Petukhova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Bulakh","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1285-9093","authenticated-orcid":false,"given":"Oxana","family":"Ryzhkova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana","family":"Nagornova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1326-8706","authenticated-orcid":false,"given":"Sofya","family":"Ionova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0972-5118","authenticated-orcid":false,"given":"Andrey","family":"Marakhonov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Dadali","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Kutsev","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1083\/jcb.201110049","article-title":"The IFT-A Complex Regulates Shh Signaling through Cilia Structure and Membrane Protein Trafficking","volume":"197","author":"Liem","year":"2012","journal-title":"J. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1007\/s00467-010-1731-7","article-title":"Ciliopathies: An Expanding Disease Spectrum","volume":"26","author":"Waters","year":"2011","journal-title":"Pediatr. Nephrol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"100937","DOI":"10.1016\/j.ymgmr.2022.100937","article-title":"Novel Mutation of IFT140 in an Infant with Mainzer-Saldino Syndrome Presenting with Retinal Dystrophy","volume":"33","author":"Yeh","year":"2022","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.ajhg.2012.03.006","article-title":"Mainzer-Saldino Syndrome Is a Ciliopathy Caused by IFT140 Mutations","volume":"90","author":"Perrault","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13630-018-0055-2","article-title":"Cellular Ciliary Phenotyping Indicates Pathogenicity of Novel Variants in IFT140 and Confirms a Mainzer-Saldino Syndrome Diagnosis","volume":"7","author":"Oud","year":"2018","journal-title":"Cilia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s13023-020-1303-2","article-title":"Compound Heterozygous IFT140 Variants in Two Polish Families with Sensenbrenner Syndrome and Early Onset End-Stage Renal Disease","volume":"15","author":"Posmyk","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1097\/MCD.0000000000000169","article-title":"The Evolving Craniofacial Phenotype of a Patient with Sensenbrenner Syndrome Caused by IFT140 Compound Heterozygous Mutations","volume":"26","author":"Bayat","year":"2017","journal-title":"Clin. Dysmorphol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"931822","DOI":"10.3389\/fgene.2022.931822","article-title":"Identical IFT140 Variants Cause Variable Skeletal Ciliopathy Phenotypes\u2014Challenges for the Accurate Diagnosis","volume":"13","author":"Wawrocka","year":"2022","journal-title":"Front. Genet."},{"key":"ref_9","first-page":"212","article-title":"Sensenbrenner Syndrome: A New Member of the Hepatorenal Fibrocystic Family","volume":"221","author":"Zaffanello","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s11604-020-00920-w","article-title":"Skeletal Ciliopathies: A Pattern Recognition Approach","volume":"38","author":"Handa","year":"2020","journal-title":"Jpn. J. Radiol."},{"key":"ref_11","first-page":"4","article-title":"\u0420\u0443\u043ao\u0432o\u0434\u0441\u0442\u0432o \u041fo \u0418\u043d\u0442\u0435\u0440\u043f\u0440\u0435\u0442\u0430\u0446\u0438\u0438 \u0414\u0430\u043d\u043d\u044b\u0445, \u041fo\u043b\u0443\u0447\u0435\u043d\u043d\u044b\u0445 \u041c\u0435\u0442o\u0434o\u043c \u041c\u0430\u0441\u0441o\u0432o\u0433o \u041f\u0430\u0440\u0430\u043b\u0435\u043b\u043b\u044c\u043do\u0433o \u0421\u0435\u043a\u0432\u0435\u043d\u0438\u0440o\u0432\u0430\u043d\u0438\u044f (Mps)","volume":"16","year":"2016","journal-title":"\u041c\u0435\u0434\u0438\u0446\u0438\u043d\u0441\u043a\u0430\u044f \u0413\u0435\u043d\u0435\u0442\u0438\u043a\u0430"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"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_13","doi-asserted-by":"crossref","first-page":"D1207","DOI":"10.1093\/nar\/gkaa1043","article-title":"The Human Phenotype Ontology in 2021","volume":"49","author":"Gargano","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1002\/humu.23539","article-title":"Whole-Genome Sequencing in Patients with Ciliopathies Uncovers a Novel Recurrent Tandem Duplication in IFT140","volume":"39","author":"Geoffroy","year":"2019","journal-title":"Hum. Mutat."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1002\/ajmg.a.61366","article-title":"Nosology and Classification of Genetic Skeletal Disorders: 2019 Revision","volume":"179","author":"Mortier","year":"2019","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1038\/s10038-021-00925-x","article-title":"High Diagnostic Yield in Skeletal Ciliopathies Using Massively Parallel Genome Sequencing, Structural Variant Screening and RNA Analyses","volume":"66","author":"Pettersson","year":"2021","journal-title":"J. Hum. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2917","DOI":"10.1002\/ajmg.a.35608","article-title":"WDR35 Mutation in Siblings with Sensenbrenner Syndrome: A Ciliopathy with Variable Phenotype","volume":"158","author":"Bacino","year":"2012","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1002\/jbmr.4035","article-title":"Functional Characterization of PHEX Gene Variants in Children with X-Linked Hypophosphatemic Rickets Shows No Evidence of Genotype\u2013Phenotype Correlation","volume":"35","author":"Zheng","year":"2020","journal-title":"J. Bone Miner Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1007\/s00467-004-1629-3","article-title":"No evidence for genotype\/phenotype correlation in NPHS1 and NPHS2 mutations","volume":"19","author":"Schultheiss","year":"2004","journal-title":"Pediatr Nephrol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/8\/1553\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:21:42Z","timestamp":1760127702000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/8\/1553"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,28]]},"references-count":19,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["genes14081553"],"URL":"https:\/\/doi.org\/10.3390\/genes14081553","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,28]]}}}