{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:14:52Z","timestamp":1790500492232,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2020,11,15]],"date-time":"2020-11-15T00:00:00Z","timestamp":1605398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Schimke immuno-osseous dysplasia (SIOD) is a rare multisystemic disorder with a variable clinical expressivity caused by biallelic variants in SMARCAL1. A phenotype\u2013genotype correlation has been attempted and variable expressivity of biallelic SMARCAL1 variants may be associated with environmental and genetic disturbances of gene expression. We describe two siblings born from consanguineous parents with a diagnosis of SIOD revealed by whole exome sequencing (WES). Results: A homozygous missense variant in the SMARCAL1 gene (c.1682G&gt;A; p.Arg561His) was identified in both patients. Despite carrying the same variant, the two patients showed substantial renal and immunological phenotypic differences. We describe features not previously associated with SIOD\u2014both patients had congenital anomalies of the kidneys and of the urinary tract and one of them succumbed to a classical type congenital mesoblastic nephroma. We performed an extensive characterization of the immunophenotype showing combined immunodeficiency characterized by a profound lymphopenia, lack of thymic output, defective IL-7R\u03b1 expression, and disturbed B plasma cells differentiation and immunoglobulin production in addition to an altered NK-cell phenotype and function. Conclusions: Overall, our results contribute to extending the phenotypic spectrum of features associated with SMARCAL1 mutations and to better characterizing the underlying immunologic disorder with critical implications for therapeutic and management strategies.<\/jats:p>","DOI":"10.3390\/ijms21228604","type":"journal-article","created":{"date-parts":[[2020,11,16]],"date-time":"2020-11-16T21:48:52Z","timestamp":1605563332000},"page":"8604","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Expanding Phenotype of Schimke Immuno-Osseous Dysplasia: Congenital Anomalies of the Kidneys and of the Urinary Tract and Alteration of NK Cells"],"prefix":"10.3390","volume":"21","author":[{"given":"Cristina","family":"Bertulli","sequence":"first","affiliation":[{"name":"Nephrology and Dialysis Unit, Department of Pediatrics, S. Orsola-Malpighi Hospital Scientific Institute for Research and Healthcare (IRCCS), 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2177-8500","authenticated-orcid":false,"given":"Antonio","family":"Marzollo","sequence":"additional","affiliation":[{"name":"Pediatric Hematology, Oncology and Stem Cell Transplant Division, Padua University Hospital, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5533-0304","authenticated-orcid":false,"given":"Margherita","family":"Doria","sequence":"additional","affiliation":[{"name":"Unit of Primary Immunodeficiency, Academic Department of Pediatrics (DPUO), Bambino Ges\u00f9 Childrens\u2019 Hospital-Scientific Institute for Research and Healthcare (IRCCS), 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9912-7997","authenticated-orcid":false,"given":"Silvia","family":"Di Cesare","sequence":"additional","affiliation":[{"name":"Unit of Primary Immunodeficiency, Academic Department of Pediatrics (DPUO), Bambino Ges\u00f9 Childrens\u2019 Hospital-Scientific Institute for Research and Healthcare (IRCCS), 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2644-7447","authenticated-orcid":false,"given":"Claudio","family":"La Scola","sequence":"additional","affiliation":[{"name":"Nephrology and Dialysis Unit, Department of Pediatrics, S. Orsola-Malpighi Hospital Scientific Institute for Research and Healthcare (IRCCS), 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Mencarelli","sequence":"additional","affiliation":[{"name":"Nephrology and Dialysis Unit, Department of Pediatrics, S. Orsola-Malpighi Hospital Scientific Institute for Research and Healthcare (IRCCS), 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Pasini","sequence":"additional","affiliation":[{"name":"Nephrology and Dialysis Unit, Department of Pediatrics, S. Orsola-Malpighi Hospital Scientific Institute for Research and Healthcare (IRCCS), 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carmen","family":"Affinita","sequence":"additional","affiliation":[{"name":"Pediatric Hematology, Oncology and Stem Cell Transplant Division, Padua University Hospital, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3963-0803","authenticated-orcid":false,"given":"Enrico","family":"Vidal","sequence":"additional","affiliation":[{"name":"Dialysis and Transplantation Unit, Pediatric Nephrology, Department of Woman\u2019s and Child\u2019s Health, University Hospital of Padua, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Magini","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of Medical and Surgical Science, S. Orsola-Malpighi Hospital_Scientific Institute for Research and Healthcare (IRCCS), 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Dimartino","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, DIMEC, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1264-057X","authenticated-orcid":false,"given":"Riccardo","family":"Masetti","sequence":"additional","affiliation":[{"name":"\u201cLalla Ser\u00e0gnoli\u201d, Hematology-Oncology Unit, Department of Pediatrics, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3914-8614","authenticated-orcid":false,"given":"Laura","family":"Greco","sequence":"additional","affiliation":[{"name":"Pediatric Radiology Unit, Department of Diagnostic and Preventive Medicine, S. Orsola-Malpighi Hospital, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Palomba","sequence":"additional","affiliation":[{"name":"Immunology Research Area\u2014Unit of Diagnostic Immunology, Unit of B-cell Pathophysiology, Department of Laboratories, IRCCS Ospedale Pediatrico Bambino Ges\u00f9, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3665-8926","authenticated-orcid":false,"given":"Francesca","family":"Conti","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Woman, Child and Urologic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0379-9562","authenticated-orcid":false,"given":"Andrea","family":"Pession","sequence":"additional","affiliation":[{"name":"\u201cLalla Ser\u00e0gnoli\u201d, Hematology-Oncology Unit, Department of Pediatrics, University of Bologna, 40138 Bologna, Italy"},{"name":"Pediatric Unit, Department of Woman, Child and Urologic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,15]]},"reference":[{"key":"ref_1","first-page":"258","article-title":"Chondroitin-6-sulfate mucopoly-saccharidosis in conjunction with lymphopenia, defective cellular immunity and the nephrotic syndrome","volume":"10","author":"Schimke","year":"1974","journal-title":"Birth Defects Orig. 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