A Novel Compound Heterozygous Mutation of the SMARCAL1 Gene Leading to Mild Schimke Immune-osseous Dysplasia: a Case Report

Overview

Journal BMC Pediatr

Publisher Biomed Central

Specialty Pediatrics

Date 2017 Dec 29

PMID 29282041

Citations 4

Authors

Shuaimei Liu

Mingchao Zhang

Mengxia Ni

Peiran Zhu

Xinyi Xia

Affiliations

Soon will be listed here.

Abstract

Background: Schimke immune-osseous dysplasia (SIOD, OMIM 242900) is characterized by spondyloepiphyseal dysplasia, T-cell deficiency, renal dysfunction and special facial features. SMARCAL1 gene mutations are determined in approximately 50% of patients diagnosed with SIOD.

Case Presentation: The case presented here is that of a 6-year-old boy who was born at 33 weeks to healthy, non-consanguineous Chinese parents. He presented with short stature (95 cm; <3rd percentile) and proteinuria. Initially suspected of having IgM nephropathy, the patient was finally diagnosed with mild Schimke immune-osseous dysplasia. One novel mutation (p.R817H) and one well-known mutation (p.R645C) was identified in the SMARCAL1 gene.

Conclusion: This report describes a clinical and genetic diagnostic model of mild SIOD. It also highlights the importance of molecular testing or clinical diagnosis and the guidance it provides in disease prognosis.

Citing Articles

Schimke immuno-osseous dysplasia. A case report in Colombia.

Orozco R, Padilla-Guzman A, Forero-Delgadillo J, Jimenez V, Pachajoa H, Parra N Mol Genet Metab Rep. 2023; 37:100995.

PMID: 37662493 PMC: 10472290. DOI: 10.1016/j.ymgmr.2023.100995.

T-cell receptor signaling in Schimke immuno-osseous dysplasia is SMARCAL1-independent.

Marin A, Jimenez-Reinoso A, Mazariegos M, Roman-Ortiz E, Regueiro J Front Immunol. 2022; 13:979722.

PMID: 36330520 PMC: 9623027. DOI: 10.3389/fimmu.2022.979722.

A novel compound heterozygous variant in leading to mild Schimke immune-osseous dysplasia identified using whole-exome sequencing.

Wang L, Li J, Wu G, Kong X J Int Med Res. 2021; 49(4):3000605211010644.

PMID: 33900868 PMC: 8829751. DOI: 10.1177/03000605211010644.

Whole Exome Sequencing Identified a Novel Biallelic Mutation in the Extremely Rare Disease SIOD.

Jin J, Wu K, Liu Z, Chen X, Jiang S, Wang Z Front Genet. 2019; 10:565.

PMID: 31275356 PMC: 6591458. DOI: 10.3389/fgene.2019.00565.

References

Schimke R, Horton W, King C . Chondroitin-6-sulphaturia, defective cellular immunity, and nephrotic syndrome. Lancet. 1971; 2(7733):1088-9. DOI: 10.1016/s0140-6736(71)90400-4. View

Pazin M, Kadonaga J . SWI2/SNF2 and related proteins: ATP-driven motors that disrupt protein-DNA interactions?. Cell. 1997; 88(6):737-40. DOI: 10.1016/s0092-8674(00)81918-2. View

Durr H, Korner C, Muller M, Hickmann V, Hopfner K . X-ray structures of the Sulfolobus solfataricus SWI2/SNF2 ATPase core and its complex with DNA. Cell. 2005; 121(3):363-73. DOI: 10.1016/j.cell.2005.03.026. View

Sanyal M, Morimoto M, Baradaran-Heravi A, Choi K, Kambham N, Jensen K . Lack of IL7Rα expression in T cells is a hallmark of T-cell immunodeficiency in Schimke immuno-osseous dysplasia (SIOD). Clin Immunol. 2015; 161(2):355-65. DOI: 10.1016/j.clim.2015.10.005. View

Carroll C, Hunley T, Guo Y, Cortez D . A novel splice site mutation in SMARCAL1 results in aberrant exon definition in a child with Schimke immunoosseous dysplasia. Am J Med Genet A. 2015; 167A(10):2260-4. PMC: 4743909. DOI: 10.1002/ajmg.a.37146. View

Elizondo L, Cho K, Zhang W, Yan J, Huang C, Huang Y . Schimke immuno-osseous dysplasia: SMARCAL1 loss-of-function and phenotypic correlation. J Med Genet. 2008; 46(1):49-59. DOI: 10.1136/jmg.2008.060095. View

Barraza-Garcia J, Rivera-Pedroza C, Belinchon A, Fernandez-Camblor C, Valenciano-Fuente B, Lapunzina P . A novel SMARCAL1 missense mutation that affects splicing in a severely affected Schimke immunoosseous dysplasia patient. Eur J Med Genet. 2016; 59(8):363-6. DOI: 10.1016/j.ejmg.2016.06.002. View

Morimoto M, Choi K, Boerkoel C, Cho K . Chromatin changes in SMARCAL1 deficiency: A hypothesis for the gene expression alterations of Schimke immuno-osseous dysplasia. Nucleus. 2016; 7(6):560-571. PMC: 5215361. DOI: 10.1080/19491034.2016.1255835. View

Zivicnjak M, Franke D, Zenker M, Hoyer J, Lucke T, Pape L . SMARCAL1 mutations: a cause of prepubertal idiopathic steroid-resistant nephrotic syndrome. Pediatr Res. 2009; 65(5):564-8. DOI: 10.1203/PDR.0b013e3181998a74. View

10.

Gorbalenya A, Koonin E, Donchenko A, Blinov V . Two related superfamilies of putative helicases involved in replication, recombination, repair and expression of DNA and RNA genomes. Nucleic Acids Res. 1989; 17(12):4713-30. PMC: 318027. DOI: 10.1093/nar/17.12.4713. View

11.

Lucke T, Kanzelmeyer N, Franke D, Hartmann H, Ehrich J, Das A . [Schimke immuno-osseous dysplasia. A pediatric disease reaches adulthood]. Med Klin (Munich). 2006; 101(3):208-11. DOI: 10.1007/s00063-006-1026-8. View

12.

Simon A, Lev A, Jeison M, Borochowitz Z, Korn D, Lerenthal Y . Novel SMARCAL1 bi-allelic mutations associated with a chromosomal breakage phenotype in a severe SIOD patient. J Clin Immunol. 2013; 34(1):76-83. DOI: 10.1007/s10875-013-9957-3. View

13.

Havas K, Whitehouse I, Owen-Hughes T . ATP-dependent chromatin remodeling activities. Cell Mol Life Sci. 2001; 58(5-6):673-82. PMC: 11337354. DOI: 10.1007/pl00000891. View

14.

Huang C, Gu S, Yu P, Yu F, Feng C, Gao N . Deficiency of smarcal1 causes cell cycle arrest and developmental abnormalities in zebrafish. Dev Biol. 2009; 339(1):89-100. DOI: 10.1016/j.ydbio.2009.12.018. View

15.

Boerkoel C, Takashima H, John J, Yan J, Stankiewicz P, Rosenbarker L . Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia. Nat Genet. 2002; 30(2):215-20. DOI: 10.1038/ng821. View

16.

Koonin E . A common set of conserved motifs in a vast variety of putative nucleic acid-dependent ATPases including MCM proteins involved in the initiation of eukaryotic DNA replication. Nucleic Acids Res. 1993; 21(11):2541-7. PMC: 309579. DOI: 10.1093/nar/21.11.2541. View

17.

Yue Z, Xiong S, Sun L, Huang W, Mo Y, Huang L . Novel compound mutations of SMARCAL1 associated with severe Schimke immuno-osseous dysplasia in a Chinese patient. Nephrol Dial Transplant. 2010; 25(5):1697-702. DOI: 10.1093/ndt/gfq071. View

18.

Clewing J, Fryssira H, Goodman D, Smithson S, Sloan E, Lou S . Schimke immunoosseous dysplasia: suggestions of genetic diversity. Hum Mutat. 2006; 28(3):273-83. DOI: 10.1002/humu.20432. View

19.

Bansbach C, Betous R, Lovejoy C, Glick G, Cortez D . The annealing helicase SMARCAL1 maintains genome integrity at stalled replication forks. Genes Dev. 2009; 23(20):2405-14. PMC: 2764496. DOI: 10.1101/gad.1839909. View

20.

Morimoto M, Yu Z, Stenzel P, Clewing J, Najafian B, Mayfield C . Reduced elastogenesis: a clue to the arteriosclerosis and emphysematous changes in Schimke immuno-osseous dysplasia?. Orphanet J Rare Dis. 2012; 7:70. PMC: 3568709. DOI: 10.1186/1750-1172-7-70. View