A novel SMARCAL1 mutation associated with a mild phenotype of Schimke immuno-osseous dysplasia (SIOD)

Abstract

BackgroundSchimke immuno-osseous dysplasia (SIOD, OMIM #242900) is an autosomal-recessive pleiotropic disorder characterized by spondyloepiphyseal dysplasia, renal dysfunction and T-cell immunodeficiency. SIOD is caused by mutations in the gene SMARCAL1.Case presentationWe report the clinical and genetic diagnosis of a 5-years old girl with SIOD, referred to our Center because of nephrotic-range proteinuria occasionally detected during the follow-up for congenital hypothyroidism. Mutational analysis of SMARCAL1 gene was performed by polymerase chain reaction (PCR) and bidirectional sequencing. Sequence analysis revealed that patient was compound heterozygous for two SMARCAL1 mutations: a novel missense change (p.Arg247Pro) and a well-known nonsense mutation (p.Glu848*).ConclusionThis report provided the clinical and genetic description of a mild phenotype of Schimke immuno-osseous dysplasia associated with nephrotic proteinuria, decreasing after combined therapy with ACE inhibitors and sartans. Our experience highlighted the importance of detailed clinical evaluation, appropriate genetic counseling and molecular testing, to provide timely treatment and more accurate prognosis.

PTX3 modulates the immunoflogosis in tumor microenvironment and is a prognostic factor for patients with clear cell renal cell carcinoma

“…PTX-3 serum levels were tested on serum samples drawn at the time of nephrectomy in the whole study population. Circulating PTX3 was measured was assayed using a commercially available ELISA Kit, according to the manufacturer's instructions (R&D Systems, Minneapolis, MN), as previously described [66,67].…”

SMARCAL1, the annealing helicase and the transcriptional co‐regulator

“…7 Mutations in SMARCAL1 are linked to Schimke immuno-osseous dysplasia (SIOD), an autosomal recessive disorder characterized by pleiotropic phenotypes. [8][9][10][11][12] In this review, we will expand on the biophysical and functional characteristics of SMARCAL1.…”

Rare case of nephrotic syndrome: Schimke syndrome

“…In more severe cases of nephrotic syndrome and/or end-stage chronic renal failure stage, renal transplantation is indicated and there are no reports of post-transplant nephrotic syndrome, although infectious and cerebrovascular complications can still occur, since the SMARCAL mutation affects many systems beyond glomeruli. 2 There is no consensus as to bone marrow transplantation as treatment for marrow involvement. 12 It has been reported that patients with SIOD generally die within the first two decades of life by: infections (23%), stroke (17%), renal failure (15%), pulmonary hypertension and congestive heart failure (15%), organ transplant complications (9%), complications of lymphoproliferative diseases (9%), gastrointestinal hemorrhage (6%), bone marrow aplasia (3%) and acute restrictive lung disease (3%).…”

“…2 The only known cause is the mutation in the SMARCAL 1 gene, HepA-related protein; however, approximately 50% of patients do not have this mutation. SMARCAL 1 is a fundamental remodeling protein for genome integrity.…”

“…The exact disease prevalence is still unknown. 2 Clinical evidence of SIOD are: spondyloepiphyseal dysplasia causing growth disorders, typical facies, nephrotic syndrome caused by focal segmental glomerulosclerosis (FSGS) and progressive renal failure, recurrent lymphopenia, T-cell immunodeficiency and pigmented nevi. 2 …”