Expanding the Clinical Features of Schimke Immuno-osseous Dysplasia: a New Patient with a Novel Variant and Novel Clinical Findings

Ceren Alavanda; Şenol Demir; Serçin Güven; Mehmet Eltan; Sevgi Bilgiç Eltan; Asena Pınar Sefer; Serim Pul; Tülay Güran; Harika Alpay; Ahmet Arman; Pınar Ata; Serap Turan

doi:10.4274/jcrpe.galenos.2024.2024-1-17

Abstract

Schimke immuno-osseous dysplasia (SIOD) (MIM:242900) is an ultra-rare, autosomal recessive, pan-ethnic pleiotropic disease. Typical findings of this syndrome are steroid-resistant nephrotic syndrome, cellular immunodeficiency, spondyloepiphyseal dysplasia (SED) and facial dysmorphism. Biallelic variants in the SMARCAL1 gene cause SIOD. The five-and-a-half-year-old female patient was evaluated because of short stature, dysmorphism, hypercalcemia, hypophosphatemia, and elevated follicle-stimulating hormone (FSH) levels. Karyotype analysis and array-CGH testing were normal. Clinical exome sequencing (CES) was performed to analyze genes associated with hypophosphatemia. No pathogenic variant was detected. The subsequent detection of proteinuria during follow-up for cross-fused ectopic left kidney ultimately facilitated the diagnosis of SIOD, although no obvious SED was detected. Re-analysis of CES revealed a novel homozygous c.2422_2427+9delinsA pathogenic variant in the SMARCAL1. The literature on SMARCAL1 gene pathogenic variants, including 125 SIOD cases from 38 articles was reviewed to investigate whether hypercalcemia, hypophosphatemia, and elevated FSH levels had been previously reported in SIOD patients. This review revealed that this was the first report of these findings in a patient with SIOD. Thus, this report expands both the phenotypic and genotypic spectrum of SIOD.

Keywords:

SMARCAL1, hypercalcemia, hypophosphatemia, ectopic kidney, gonadal dysfunction

Introduction

Schimke immuno-osseous dysplasia (SIOD) (MIM: 242900) is an ultra-rare, autosomal recessive, pan-ethnic pleiotropic disease. The prevalence of SIOD is estimated to be 1 in 1-3 million live births in the USA (1). This syndrome was first described as chondroitin-6-sulfate mucopolysaccharidosis (2). However, after further studies, mucopolysaccharidosis was excluded (3). The main findings of this syndrome are steroid-resistant nephrotic syndrome, immunodeficiency, and spondyloepiphyseal dysplasia (SED). The short stature observed in almost all patients is due to the SED (4). Renal disease, mostly due to focal segmental glomerulosclerosis (FSGS), is progressive and eventually leads to end-stage renal failure. Defective cellular immunity is the cause of the associated immunodeficiency. Patients also exhibit typical phenotypic features, such as fine hair, a triangular face, a depressed nasal bridge, a bulbous nasal tip, microdontia, a short neck, a short trunk, hyperpigmented macules, and a protruding abdomen. In 2002, it was discovered that biallelic pathogenic variants in the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A-like 1 gene (SMARCAL1) caused this syndrome (5).

Herein, we present a patient with SIOD who exhibited an atypical clinical presentation characterized by hypercalcemia and hypophosphatemia, resembling osteopenia of prematurity, along with elevated follicle-stimulating hormone (FSH) levels indicative of primary gonadal failure. Furthermore, we conducted a review of all genetically confirmed cases of SIOD, providing an occurrence ratio of clinical and laboratory findings in comparison with our patient.

Diagnostic Insights in Schimke Immuno-osseous Dysplasia

A one-and-a-half-year-old female was referred to the medical genetics outpatient clinic with disproportionate short stature and renal failure. She was the second child of a 33-year-old mother and 36-year-old father, both of whom were healthy. Although there was no consanguinity between her parents, they both came from the same small village. Family history was unremarkable. She was born at 30 gestational weeks with a birth weight of 945 g [-2.1 standard deviation score (SDS)] and birth length of 35 cm (-2 SDS), and was hospitalized in the neonatal intensive care unit (NICU) for three months due to prematurity. At that time, patent ductus arteriosus, patent foramen ovale, and atrial septal defect were detected by echocardiography. Her cranial ultrasonography (USG) was normal. She passed the hearing test and her ophthalmologic examination revealed no retinopathy of prematurity.

The timeline of the patient’s medical history and diagnostic procedures, and results are shown in Figure 1. At the initial presentation, at the age of 7 months, she was referred to the pediatric endocrinology clinic for hypercalcemia. On physical examination, height was 58 cm (-3.9 SDS), weight was 4.5 kg (-4.4 SDS), and head circumference was 38 cm (-4.2 SDS), while mid-parental height was at -1 SDS. The dysmorphic examination revealed that she had fine and sparse hair, microcephaly, prominent forehead, synophrisis, upslanting palpebral fissures, malar hypoplasia, depressed nasal bridge, bulbous nasal tip, long philtrum, thin upper lip, retrognathia, everted lower lip, microdontia, posteriorly rotated and low set ears, anteverted ears, short neck, short trunk, hyperpigmented macules on the trunk, protruding abdomen, tapering fingers, and brachydactyly (Figure 2). External genitalia were normal.

The laboratory evaluation revealed the following results: calcium (Ca) of 11.6 mg/dL [normal range (NR) 8.7-11], PO₄ of 3.2 mg/dL (NR 5.0-7.8), alkaline phosphatase (ALP) of 1122 U/L (NR 116-450), 25-OH vitamin D of 24.4 μg/L (NR 30-100), parathyroid hormone of 6.2 ng/L (NR 15-65), creatinine (Cre) of 0.19 mg/dL (NR 0.0-0.42), magnesium of 2.4 mg/dL (NR 1.8-2.6), urinary Ca/Cre ratio of 0.4 mg/mg (NR 0.03-0.8), tubular phosphate resorption of 98% (NR 85-100), and tubular maximum for phosphate/glomerular filtration rate of 5.45 (NR 4.8-8). The laboratory and wrist X-ray were consistent with the osteopenia of prematurity and rickets, which were related to phosphate deficiency. Phosphate replacement therapy was initiated and continued for five months, resulting in the normalization of biochemical parameters and improvement in radiological findings (Figure 2).

The patient had not demonstrated catch-up growth and exhibited poor growth velocity. She began to sit independently at 10 months old and started walking at 18 months. She also had her first words at 18 months.

Endocrinological evaluation of short stature at the age of 19 months revealed low levels of insulin-like growth factor-1 (IGF-1) (-2 SDS) and IGF binding protein-3 (IGFBP-3) (-2.4 SDS) along with an elevated FSH level (24 U/L). Biochemical parameters, including renal function and celiac-associated antibodies showed no abnormality. The bone age was consistent with the chronological age (Figure 2a.3). Turner syndrome was considered as a potential diagnosis due to the presence of short stature, an ectopic kidney, and elevated FSH levels. However, karyotype analysis and array-CGH testing demonstrated a 46,XX karyotype with no deletion or duplication. Furthermore, a growth hormone (GH) stimulation test with glucagon showed a high basal GH level (17.6 ng/mL) and an exaggerated peak GH response (32 ng/mL) with consistently elevated GH levels throughout the test. One year after the first elevated FSH measurement, FSH was 14.1 U/L, luteinizing hormone was <0.2 U/L and estradiol was 13.3 ng/L at the age of 2.5 years. The first The first elevation in thyroid-stimulating hormone (TSH) was detected at age 3 years and had worsened by the age of 3.5 years, with levels of 6.44 mIU/L and 12.80 mIU/L (NR 0.70-5.97), respectively.

Furthermore, USG of the urinary tract showed a cross-fused ectopic left kidney at initial evaluation. The patient was referred to pediatric nephrology. At nephrological follow-up of the patient, she had experienced recurrent urinary tract infections. She was diagnosed with nephrotic syndrome at the age of 1.5 years. She was treated with albumin infusions, diuretics, angiotensin-converting enzyme inhibitors, and corticosteroids but failed to respond. The patient presented with severe decompensation of nephrotic syndrome that required peritoneal dialysis for 10 months and she received a kidney transplant from her uncle when she was 4 years old. The patient was not deemed to need a renal biopsy since she had received a genetic diagnosis. The patient’s initial blood pressure measurement was 92/54 mmHg, while at the last measurement, it was 118/84 mmHg (NR 105/63).

Nephrological evaluation revealed hemoglobin 15.6 g/dL (NR 12-16), hematocrit 46.7% (NR 36-48%), mean corpuscular volume 80.9 fL (NR 80-100), white blood cell 7.3x10³/μL (NR 4.5-11x10³), mild lymphopenia of 1x10³/μL (NR 2.1-7.8x10³) (5), platelet count 293x10³/μL (NR 150-450x10³), hypoalbuminemia with an albumin of 2.2 g/dL (NR 3.4-5.4), high total cholesterol level of 382 mg/dL (NR <200) and hypertriglyceridemia of 253 mg/dL (NR <150). Urinalysis demonstrated 3+ proteinuria. Spot urine protein was 1043 mg/dL (NR 0-10), urine Cre 37 mg/dL (NR 20-275), and the urine protein/Cre ratio was calculated as 28.1 mg/mg Cre (NR <0.5). Serum complement C3 level was 197 mg/dL (NR 80-120) and C4 level was 59 mg/dL (NR 10-40).

Although no obvious bone dysplasia was initially detected on hand X-rays, SIOD was considered as a potential diagnosis after the development of nephrotic syndrome. However, a more comprehensive skeletal survey revealed certain skeletal abnormalities, including ovoid vertebral bodies and shallow acetabular fossae with laterally displaced femoral heads (Figure 2c, 2d). Notably, there were no epiphyseal changes observed. Subsequent X-rays taken at the age of five-and-a-half-years displayed mild platyspondyly, metaphyseal widening of the long bones, and osteopenia with metaphyseal sclerosis (Figure 2d.1).

Immunological analyses at the age of 34 months revealed mild lymphopenia of 1.3x10³/μL, low serum IgG of 157 mg/dL (NR 604-1921), but normal levels of IgA 58 mg/dL (NR 26-228), and IgM 167 mg/dL (NR 71-235). Serum IgE level was moderately elevated as 149 IU/mL. The patient also had anemia and thrombocytopenia. Responses to protein antigens, including hepatitis B, mumps IgG were negative, and measles, varicella, and rubella IgG were positive. Lymphocyte subgroup analysis showed severe CD3+ T, CD4+ T, and CD8+ T lymphopenia accompanied by decreased naive and increased memory CD4+ and CD8+ T cells. Elevated CD19+ B lymphocyte numbers were detected, while CD16+ CD56+ NK cell numbers were normal. Although the patient had no history of recurrent infections other than recurrent urinary tract infections, concomitant prophylactic antibiotics and immunoglobulin infusions were administered every 3 weeks with a diagnosis of combined immunodeficiency. The clinical findings of the patient are summarized in Table 1.

After obtaining informed written consent from the patient’s parents, DNA was isolated from her peripheral blood using QIAamp DNA Mini Kit (Qiagen, Hilden, Germany). Clinical exome sequencing (CES) was performed via next-generation sequencing (Illumina Nextseq 500) using Sophia Clinical Exome Solution V2. Data were analyzed through the Sophia DDM-V4 platform. Non-synonymous (missense, nonsense, in-frame, frameshift) variants with minor allele frequency less than 1.0% in population studies (1000 Genomes-1000G, Exome Aggregation Consortium database-ExAC, and Genome Aggregation Database-gnomAD) were filtered. American College of Medical Genetics and Genomics (ACMG) criteria were also applied. Retained variants were searched for in ClinVar and the Human Genome Mutation Database (HGMD). Segregation analyses were also performed via Illumina Nextseq 500. Molecular analysis revealed a novel homozygous c.2422_2427+9delinsA (NM_001127207) variant in the SMARCAL1 gene (Figure 3a). It was localized at the donor site of the 15^th exon. This variant was not reported in Clinvar and HGMD. According to ACMG criteria, this variant was pathogenic (PVS1, PM2, PP3). Segregation analysis revealed that her parents were heterozygous for this variant (Figure 3b, 3c). Given the presentation at the age of seven months with hypophosphatemia requiring phosphate replacement, genetic causes of hypophosphatemia were considered. No variant was detected in the customized panel containing PHEX, DMP1, FGF23, ANKH, CYP27B1, CYP2R1, VDR, CYP3A4, CYP24A1, SLC34A1, SLC34A3, KL, GALNT3, CLCN5, SLC2A2, OCRL, FAM20C, FGFR1, ABCC6, ALPL, EXT1, SLC9A3R1, AVPR2 genes selected from CES.

Discussion

SIOD is a pleiotropic disorder with typical clinical findings of short stature, SED, immune deficiency, renal involvement, and typical dysmorphic findings. However, the diagnosis of SIOD can be challenging before the occurrence of renal findings, as observed in the presented case. The presented patient was born prematurely with intrauterine growth retardation (IUGR) and required prolonged hospitalization in the NICU. Subsequently, she presented with hypercalcemia related to the hypophosphatemia and needed prolonged (5 months) phosphate replacement. Genetic analysis for hypophosphatemia found no etiology, and she was accepted as having osteopenia of prematurity. Later follow-up demonstrated no catch-up growth and the presence of elevated FSH, along with an ectopic kidney, suggested Turner syndrome. However, further investigation, including a normal female karyotype and array-CGH testing did not confirm this diagnosis. Nephrological follow-up for the patient, focusing on her cross-fused ectopic left kidney and recurrent urinary tract infections, ultimately led to the early diagnosis of proteinuria and SIOD.

When we reviewed all published genetically-confirmed cases of SIOD, all cases exhibited short stature, and almost all (94.4%) had IUGR. In addition, proteinuria was a consistent feature in all cases, serving as the primary indicator leading to the diagnosis of SIOD, as observed in the presented case. Although short stature is a universal feature of SIOD, only a few patients have had their GH/IGF-1 axis evaluated. Almost all of the evaluated cases demonstrated normal GH levels on GH stimulation tests (7, 8, 9, 10). Furthermore, when the patients were treated with GH, they responded poorly to GH treatment (4, 6, 11, 12, 13) even in the case of low GH levels at GH stimulation tests (14). The presented patient, however, showed high basal GH levels and an exaggerated peak GH response to stimulation, along with low IGF-1 and IGFBP-3 levels, indicative of GH resistance. When all reported patients were evaluated from this perspective, although most GH stimulation tests were described as normal (exact values not provided), at least one patient had GH levels similar to ours (9). However, IGF-1 and IGFBP-3 levels were not mentioned in any of the other patients. In light of the poor response to GH treatment, normal or high GH levels, and low IGF-1 and IGFBP-3 levels in our case, SIOD may be considered a condition of GH resistance related to the primary disease. Furthermore, the final height of patients with SIOD ranged from 110 to 165 cm for males and from 107 cm to 143 cm for females (6, 15). Table 1 presents a comprehensive overview of all reported findings in the literature, along with the details of the presented case.

Primary gonadal failure and elevated FSH levels had not been previously reported in any SIOD patients. The FSH level was reported only once in a 14-year-old male patient and was found to be normal (9). However, cryptorchidism has been reported in five patients and may be a sign of hypogonadism (12, 15, 16, 17, 18). Furthermore, SMARCAL1 expression has been reported in fetal ovaries and testis (20). Therefore, pathogenic variants in this gene may plausibly lead to gonadal dysfunction. The reason for gonadal failure remaining unrecognized in SIOD could be due to the severity of renal or other systemic diseases and renal transplantation. More detailed laboratory studies are required in other cases of SIOD for further explanation of this issue. Unfortunately, although our patient had persistently elevated FSH levels, we did not measure anti-Mullerian hormone.

The other features we report for the first time here are hypercalcemia, hypophosphatemia and rickets in SIOD. However, these features may not be inherent to SIOD and could be a co-occurrence related to prematurity and insufficient phosphate intake.

The renal phenotype of SIOD is steroid-resistant nephrotic syndrome, which is progressive and often leads to end-stage renal failure. The main renal histopathology is FSGS; however, minimal glomerular lesions and podocytic infolding glomerulopathy have also been detected (21, 22). Our patient exhibited an additional renal phenotype, namely crossed-fused ectopic kidney. Our literature review of a total of 125 genetically confirmed patients revealed crossed-fused ectopic kidney in two other SIOD patients (19, 23). Furthermore, one patient with an ectopic kidney (24) and another patient with unilateral renal agenesis (10) have been reported. SMARCAL1 expression is known to be high in fetal kidneys and collecting ducts (23). Therefore, the association between SMARCAL1 pathogenic variants and renal malformations is an expected finding. As suggested by Dekel et al. (23), this finding may have been overlooked in some reports. Evaluating SIOD patients for renal malformations will contribute to our understanding of whether renal malformations are incidental findings or a rare component of SIOD.

The clinical presentation or progression of SIOD is classified as either severe or mild (4). In severely affected patients, IUGR, neurologic manifestations such as cerebral infarction and transient ischemic attack, hypothyroidism, and bone marrow failure are observed more frequently (6). End-stage renal failure can occur at an earlier age in severely affected patients and most die within the first 15 years of life (6). The most common causes of death are severe infections, cerebral ischemia, and renal failure (4). The immune phenotype is predominantly characterized by lymphopenia and T cell failure, leading to recurrent infections, which are one of the most important causes of death (4). The presence of IUGR, early-onset renal failure, elevated TSH levels, and immunodeficiency in our patient, consistent with a severe phenotype, leads us to anticipate that the patient could experience neurological complications in the future. Moreover, the detection of a truncating variant in the presented patient indicated a severe phenotype. Patients with biallelic non-truncating variants tend to have a milder phenotype, although a strict genotype-phenotype correlation has not been found in SIOD patients. There was no significant difference observed between patients carrying truncating and non-truncating variants, particularly concerning the renal phenotype. However, it has been demonstrated that patients with biallelic truncating mutations exhibit higher mortality rates than those with biallelic missense variants (4). Furthermore, different clinical severities have been observed in two siblings carrying the same variant, indicating intra-familial variability (11).

The SMARCAL1 gene contains 18 exons and encodes a 954 amino acid protein. SMARCAL1 protein is highly conserved and belongs to the sucrose non-fermenting 2 (SNF2) family (25). It functions as an ATP-dependent chromatin remodeling protein involved in various biological activities, such as replication, transcription, and DNA damage response. The protein contains four functionally important domains: HepA-related protein 1 (HARP1, 226-303 amino acids), HARP2 (327-398 amino acids), helicase ATP-binding domain (445-600 amino acids), and helicase C-terminal domain (716-869 amino acids). As of June 25, 2023, the HGMD lists 150 pathogenic variants in the SMARCAL1 gene, with the majority being truncating variants. SIOD-related variants are depicted in Figure 4 with many pathogenic variants located within two helicase domains, similar to the variant detected in our report.

In conclusion, we present a patient with SIOD who exhibited an atypical clinical presentation characterized by hypercalcemia and hypophosphatemia, resembling osteopenia of prematurity, along with elevated FSH levels indicating primary gonadal failure. We identified a novel, homozygous indel variant in the donor splice site of the SMARCAL1 gene. This report expands both the phenotypic and genotypic spectrum of SIOD.

Acknowledgments

We would like to thank the patient and her parents for their contributions.

Authorship Contributions

Concept: Ceren Alavanda, Serap Turan, Design: Serap Turan, Data Collection or Processing: Serçin Güven, Mehmet Eltan, Sevgi Bilgiç Eltan, Asena Pınar Sefer, Serim Pul, Tülay Güran, Harika Alpay, Ahmet Arman, Pınar Ata, Analysis or Interpretation: Ceren Alavanda, Şenol Demir, Pınar Ata, Literature Search: Ceren Alavanda, Writing: Ceren Alavanda, Serap Turan.

Conflict of Interest: One author of this article, Serap Turan, is a member of the Editorial Board of the Journal of Clinical Research in Pediatric Endocrinology. However, she did not involved in any stage of the editorial decision of the manuscript. The editors who evaluated this manuscript are from different institutions.

Financial Disclosure: The authors declared that this study received no financial support.

References

Santangelo L, Gigante M, Netti GS, Diella S, Puteo F, Carbone V, Grandaliano G, Giordano M, Gesualdo L. A novel SMARCAL1 mutation associated with a mild phenotype of Schimke immuno-osseous dysplasia (SIOD). BMC Nephrol. 2014;15:41.

Schimke RN, Horton WA, King CR. Chondroitin-6-sulphaturia, defective cellular immunity, and nephrotic syndrome. Lancet. 1971;2:1088-1089.

Spranger J, Hinkel GK, Stöss H, Thoenes W, Wargowski D, Zepp F. Schimke immuno-osseous dysplasia: a newly recognized multisystem disease. J Pediatr. 1991;119:64-72.

Lipska-Ziętkiewicz BS, Gellermann J, Boyer O, Gribouval O, Ziętkiewicz S, Kari JA, Shalaby MA, Ozaltin F, Dusek J, Melk A, Bayazit AK, Massella L, Hyla-Klekot L, Habbig S, Godron A, Szczepańska M, Bieniaś B, Drożdż D, Odeh R, Jarmużek W, Zachwieja K, Trautmann A, Antignac C, Schaefer F; PodoNet Consortium. Low renal but high extrarenal phenotype variability in Schimke immuno-osseous dysplasia. PLoS One. 2017;12:180926.

Besci Ö, Başer D, Öğülür İ, Berberoğlu AC, Kıykım A, Besci T, Leblebici A, Ellidokuz H, Boran P, Özek E, Haklar G, Özen A, Barış S, Aydıner E. Reference values for T and B lymphocyte subpopulations in Turkish children and adults. Turk J Med Sci. 202130;51:1814-1824.

Boerkoel CF, O’Neill S, André JL, Benke PJ, Bogdanovíć R, Bulla M, Burguet A, Cockfield S, Cordeiro I, Ehrich JH, Fründ S, Geary DF, Ieshima A, Illies F, Joseph MW, Kaitila I, Lama G, Leheup B, Ludman MD, McLeod DR, Medeira A, Milford DV, Ormälä T, Rener-Primec Z, Santava A, Santos HG, Schmidt B, Smith GC, Spranger J, Zupancic N, Weksberg R. Manifestations and treatment of Schimke immuno-osseous dysplasia: 14 new cases and a review of the literature. Eur J Pediatr. 2000;159:1-7.

Yue Z, Xiong S, Sun L, Huang W, Mo Y, Huang L, Jiang X, Chen S, Hu B, Wang Y. Novel compound mutations of SMARCAL1 associated with severe Schimke immuno-osseous dysplasia in a Chinese patient. Nephrol Dial Transplant. 2010;25:1697-1702

Liu S, Zhang M, Ni M, Zhu P, Xia X. A novel compound heterozygous mutation of the SMARCAL1 gene leading to mild Schimke immune-osseous dysplasia: a case report. BMC Pediatr. 2017;17:217.

Wang L, Li J, Wu G, Kong X. A novel compound heterozygous variant in SMARCAL1 leading to mild Schimke immune-osseous dysplasia identified using whole-exome sequencing. J Int Med Res. 2021;49:3000605211010644.

Zieg J, Krepelova A, Baradaran-Heravi A, Levtchenko E, Guillén-Navarro E, Balascakova M, Sukova M, Seeman T, Dusek J, Simankova N, Rosik T, Skalova S, Lebl J, Boerkoel CF. Rituximab resistant evans syndrome and autoimmunity in Schimke immuno-osseous dysplasia. Pediatr Rheumatol Online J. 2011;9:27.

Lücke T, Billing H, Sloan EA, Boerkoel CF, Franke D, Zimmering M, Ehrich JH, Das AM. Schimke-immuno-osseous dysplasia: new mutation with weak genotype-phenotype correlation in siblings. Am J Med Genet A. 2005;135:202-205.

Woo HA, Kim SH, Ahn YH, Min SI, Ha J, Ha IS, Cheong HI, Kang HG. Clinical course of post-kidney transplant Schimke immuno-osseous dysplasia. Pediatr Transplant. 2023;27:14605.

Barraza-García J, Rivera-Pedroza CI, Belinchón A, Fernández-Camblor C, Valenciano-Fuente B, Lapunzina P, Heath KE. A novel SMARCAL1 missense mutation that affects splicing in a severely affected Schimke immunoosseous dysplasia patient. Eur J Med Genet. 2016;59:363-366.

Beleford DT, Diab M, Qubty WF, Malloy MJ, Long RK, Shieh JT. Schimke immunoosseous dysplasia and management considerations for vascular risks. Am J Med Genet A. 2019;179:1246-1252.

Lücke T, Franke D, Clewing JM, Boerkoel CF, Ehrich JH, Das AM, Zivicnjak M. Schimke versus non-Schimke chronic kidney disease: an anthropometric approach. Pediatrics. 2006;118:400-407.

Taha D, Boerkoel CF, Balfe JW, Khalifah M, Sloan EA, Barbar M, Haider A, Kanaan H. Fatal lymphoproliferative disorder in a child with Schimke immuno-osseous dysplasia. Am J Med Genet A. 2004;131:194-199.

Düzova A, Gülhan B, Topaloğlu R, Özaltın F, Cengiz AB, Yetimakman AF, Doğru D, Güçer Ş, Beşbaş N. BK virus associated nephropathy and severe pneumonia in a kidney transplanted adolescent with Schimke immuneosseous- dysplasia. Turk J Pediatr. 2019;61:111-116.

Babaei AH, Inaloo S, Basiratnia M. Schimke Immuno-osseous Dysplasia: A Case Report. Indian J Nephrol. 2019;29:291-294.

Baradaran-Heravi A, Lange J, Asakura Y, Cochat P, Massella L, Boerkoel CF. Bone marrow transplantation in Schimke immuno-osseous dysplasia. Am J Med Genet A. 2013;161:2609-2613.

Stelzer G, Rosen N, Plaschkes I, Zimmerman S, Twik M, Fishilevich S, Stein TI, Nudel R, Lieder I, Mazor Y, Kaplan S, Dahary D, Warshawsky D, Guan-Golan Y, Kohn A, Rappaport N, Safran M, Lancet D. The GeneCards suite: from gene data mining to disease genome sequence analyses. Curr Protoc Bioinformatics. 2016;54:30-33.

Zivicnjak M, Franke D, Zenker M, Hoyer J, Lücke T, Pape L, Ehrich JH. SMARCAL1 mutations: a cause of prepubertal idiopathic steroid-resistant nephrotic syndrome. Pediatr Res. 2009;65:564-568.

Xiong S, Shuai L, Li X, Dang X, Wu X, He Q. Podocytic infolding in Schimke immuno-osseous dysplasia with novel SMARCAL1 mutations: a case report. BMC Nephrol. 2020;21:170.

Dekel B, Metsuyanim S, Goldstein N, Pode-Shakked N, Kovalski Y, Cohen Y, Davidovits M, Anikster Y. Schimke immuno-osseous dysplasia: expression of SMARCAL1 in blood and kidney provides novel insight into disease phenotype. Pediatr Res. 2008;63:398-403.

Bertulli C, Marzollo A, Doria M, Di Cesare S, La Scola C, Mencarelli F, Pasini A, Affinita MC, Vidal E, Magini P, Dimartino P, Masetti R, Greco L, Palomba P, Conti F, Pession A. Expanding phenotype of Schimke immuno-osseous dysplasia: congenital anomalies of the kidneys and of the urinary tract and alteration of NK cells. Int J Mol Sci. 2020;21:8604.

Coleman MA, Eisen JA, Mohrenweiser HW. Cloning and characterization of HARP/SMARCAL1: a prokaryotic HepA-related SNF2 helicase protein from human and mouse. Genomics. 2000;65:274-282.

Samanta D, Ramakrishnaiah R. Diffuse carotid arteriosclerosis and stroke in a patient with Schimke immuno-osseous dysplasia. Pediatr Neurol. 2017;71:82-83.

Morimoto M, Kérourédan O, Gendronneau M, Shuen C, Baradaran-Heravi A, Asakura Y, Basiratnia M, Bogdanovic R, Bonneau D, Buck A, Charrow J, Cochat P, Dehaai KA, Fenkçi MS, Frange P, Fründ S, Fryssira H, Keller K, Kirmani S, Kobelka C, Kohler K, Lewis DB, Massella L, McLeod DR, Milford DV, Nobili F, Olney AH, Semerci CN, Stajic N, Stein A, Taque S, Zonana J, Lücke T, Hendson G, Bonnaure-Mallet M, Boerkoel CF. Dental abnormalities in Schimke immuno-osseous dysplasia. J Dent Res. 2012;91:29-37.

Finsen SH, Tepel M, Neland M, Rittig S, Thiesson HC. Successful low-dose immunotherapy after kidney transplantation in a 10-year-old girl with Schimke immuno-osseous dysplasia. Pediatr Transplant. 2023;27:14495.

Orozco RAP, Padilla-Guzmán A, Forero-Delgadillo JM, Jiménez VAO, Pachajoa H, Parra NJV, Restrepo JM. Schimke immuno-osseous dysplasia. A case report in Colombia. Mol Genet Metab Rep. 2023;37:100995.

Malhotra R, Sharma M, Dwivedi A, Kalra S. A case of Schimke immunoosseous dsplasia caused by large deletion of SMARCAL1 gene. Indian J Endocrinol Metab. 2021;25:358-360.

Prato G, De Grandis E, Mancardi MM, Cordani R, Giacomini T, Pisciotta L, Uccella S, Severino M, Tortora D, Pavanello M, Bertamino M, Verrina E, Caridi G, Di Rocco M, Nobili L. Schimke immuno-osseous dysplasia, two new cases with peculiar EEG pattern. Brain Dev. 2020;42:408-413.

Jin J, Wu K, Liu Z, Chen X, Jiang S, Wang Z, Li W. Whole exome sequencing identified a novel biallelic SMARCAL1 mutation in the extremely rare disease SIOD. Front Genet. 2019;10:565

Power BD, Walsh KP, Awan A, Waldron M, O’Grady MJ. Klippel-Feil syndrome as a novel feature of Schimke immunoosseous dysplasia. Am J Med Genet A. 2019;179:862-863.

Haffner DN, Rollins NK, Dowling MM. Reversible cerebral vasoconstriction syndrome: a novel mechanism for neurological complications in Schimke immuno-osseous dysplasia. Pediatr Neurol. 2019;92:67-70.

Carroll C, Badu-Nkansah A, Hunley T, Baradaran-Heravi A, Cortez D, Frangoul H. Schimke immunoosseous dysplasia associated with undifferentiated carcinoma and a novel SMARCAL1 mutation in a child. Pediatr Blood Cancer. 2013;60:88-90.

Carroll C, Hunley TE, 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;167:2260-2264.

Sauerstein K, Schroth M, Amann K, Hoyer J, Singer H, Rauch A, Dötsch J. Pulmonary embolism--a rare complication of Schimke immunoosseous dysplasia. Eur J Pediatr. 2007;166:1285-1288.

Clewing JM, Fryssira H, Goodman D, Smithson SF, Sloan EA, Lou S, Huang Y, Choi K, Lücke T, Alpay H, André JL, Asakura Y, Biebuyck-Gouge N, Bogdanovic R, Bonneau D, Cancrini C, Cochat P, Cockfield S, Collard L, Cordeiro I, Cormier-Daire V, Cransberg K, Cutka K, Deschenes G, Ehrich JH, Fründ S, Georgaki H, Guillen-Navarro E, Hinkelmann B, Kanariou M, Kasap B, Kilic SS, Lama G, Lamfers P, Loirat C, Majore S, Milford D, Morin D, Ozdemir N, Pontz BF, Proesmans W, Psoni S, Reichenbach H, Reif S, Rusu C, Saraiva JM, Sakallioglu O, Schmidt B, Shoemaker L, Sigaudy S, Smith G, Sotsiou F, Stajic N, Stein A, Stray-Pedersen A, Taha D, Taque S, Tizard J, Tsimaratos M, Wong NA, Boerkoel CF. Schimke immunoosseous dysplasia: suggestions of genetic diversity. Hum Mutat. 2007;28:273-283.

Bökenkamp A, deJong M, van Wijk JA, Block D, van Hagen JM, Ludwig M. R561C missense mutation in the SMARCAL1 gene associated with mild Schimke immuno-osseous dysplasia. Pediatr Nephrol. 2005;20:1724-1728.

Mobeireek A, Saleemi S, Khalid M, Imtiaz F, Almutairy EA. Tracheobronchial anomalies in a patient with Schimke immuno-osseous dysplasia (SIOD). Am J Med Genet A. 2015;167:434-437.

Simon AJ, Lev A, Jeison M, Borochowitz ZU, Korn D, Lerenthal Y, Somech R. Novel SMARCAL1 bi-allelic mutations associated with a chromosomal breakage phenotype in a severe SIOD patient. J Clin Immunol. 2014;34:76-83.

Basiratnia M, Baradaran-Heravi A, Yavarian M, Geramizadeh B, Karimi M. Non-hodgkin lymphoma in a child with schimke immuno-osseous dysplasia. Iran J Med Sci. 2011;36:222-225.

Hara-Isono K, Matsubara K, Hamada R, Shimada S, Yamaguchi T, Wakui K, Miyazaki O, Muroya K, Kurosawa K, Fukami M, Ogata T, Kosho T, Kagami M. A patient with Silver-Russell syndrome with multilocus imprinting disturbance, and Schimke immuno-osseous dysplasia unmasked by uniparental isodisomy of chromosome 2. J Hum Genet. 2021;66:1121-1126.

Lou S, Lamfers P, McGuire N, Boerkoel CF. Longevity in Schimke immuno-osseous dysplasia. J Med Genet. 2002;39:922-925.