Schimke-immuno-osseous dysplasia: new mutation with weak genotype-phenotype correlation in siblings

Schimke-immuno-osseous dysplasia (SIOD) is a multisystem disorder with the following consistent clinical features: spondyloepiphyseal dysplasia with disproportional growth deficiency, nephrotic syndrome with focal and segmental glomerulosclerosis, and defective cellular immunity. Transitory ischemic attacks due to vaso-occlusive processes are complications in some patients with severe SIOD. Recently, mutations of SMARCAL1, which encodes a putative chromatin remodelling protein, have been associated with SIOD. Patients with milder disease were observed to harbor a missense mutation on each allele, whereas patients with a severe form of the disease were predicted to have at least one allele with a nonsense, frameshift or splicing mutation. We report two brothers who are both compound heterozygous for the mutations 836 T>C and 2542 G>T detected in exons 4 and 17, respectively. We demonstrate the lack of genotype-phenotype correlation in these patients as one brother shows some features of the severe form while the other does not. Neither clinical nor molecular findings can fully predict the clinical course of SIOD.