Expanding Phenotype of Schimke Immuno-Osseous Dysplasia: Congenital Anomalies of the Kidneys and of the Urinary Tract and Alteration of NK Cells

• Published in: International journal of molecular sciences 2020-11, Vol.21 (22), p.8604
• Main Authors: Bertulli, Cristina, Marzollo, Antonio, Doria, Margherita, Di Cesare, Silvia, La Scola, Claudio, Mencarelli, Francesca, Pasini, Andrea, Affinita, Maria Carmen, Vidal, Enrico, Magini, Pamela, Dimartino, Paola, Masetti, Riccardo, Greco, Laura, Palomba, Patrizia, Conti, Francesca, Pession, Andra
• Format: Article
• Language: English
• Subjects: Age; Amino Acid Substitution; Arteriosclerosis - diagnostic imaging; Arteriosclerosis - genetics; Arteriosclerosis - immunology; Cell differentiation; congenital; Congenital anomalies; Congenital defects; Congenital diseases; consanguinity; DNA Helicases - genetics; DNA Helicases - immunology; DNA methylation; Dysplasia; Female; Gene expression; Genotype & phenotype; Genotypes; hereditary; Humans; Hypothyroidism; immune system diseases; Immunodeficiency; Immunoglobulins; Immunological diseases; Immunology; Interleukin-7 Receptor alpha Subunit - genetics; Interleukin-7 Receptor alpha Subunit - immunology; Kidney - abnormalities; Kidney - diagnostic imaging; Kidney - immunology; Kidney diseases; Kidneys; Killer Cells, Natural - immunology; Leukopenia; Lymphopenia; Male; Mutation; Mutation, Missense; neonatal diseases and abnormalities; Nephroma, Mesoblastic - diagnostic imaging; Nephroma, Mesoblastic - genetics; Nephroma, Mesoblastic - immunology; Nephrotic Syndrome - diagnostic imaging; Nephrotic Syndrome - genetics; Nephrotic Syndrome - immunology; Osteochondrodysplasias - diagnostic imaging; Osteochondrodysplasias - genetics; Osteochondrodysplasias - immunology; Patients; Phenotype; Phenotypes; Plasma cells; Primary Immunodeficiency Diseases - diagnostic imaging; Primary Immunodeficiency Diseases - genetics; Primary Immunodeficiency Diseases - immunology; Pulmonary Embolism - diagnostic imaging; Pulmonary Embolism - genetics; Pulmonary Embolism - immunology; Thymus; Urinary tract; Urinary Tract - abnormalities; Urinary Tract - diagnostic imaging; Urinary Tract - immunology; Whole Genome Sequencing
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21228604

Schimke immuno-osseous dysplasia (SIOD) is a rare multisystemic disorder with a variable clinical expressivity caused by biallelic variants in . A phenotype-genotype correlation has been attempted and variable expressivity of biallelic 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 gene (c.1682G>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-both 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-7Rα 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 mutations and to better characterizing the underlying immunologic disorder with critical implications for therapeutic and management strategies.