Abstract
Schimke immuno-osseous dysplasia (SIOD, MIM 242900) is an autosomal-recessive pleiotropic disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction and T-cell immunodeficiency1,2,3. Using genome-wide linkage mapping and a positional candidate approach, we determined that mutations in SMARCAL1 (SWI/SNF2-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a–like 1), are responsible for SIOD. Through analysis of data from persons with SIOD in 26 unrelated families, we observed that affected individuals from 13 of 23 families with severe disease had two alleles with nonsense, frameshift or splicing mutations, whereas affected individuals from 3 of 3 families with milder disease had a missense mutation on each allele. These observations indicate that some missense mutations allow retention of partial SMARCAL1 function and thus cause milder disease.
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Acknowledgements
We thank the families described for their cooperation and H. Bellen for critical review of this manuscript. H.T. is a recipient of a postdoctoral fellowship from the Charcot–Marie–Tooth Association. This study was supported in part by the Kleberg Foundation and by grants from the US National Institute of Diabetes, Digestive, and Kidney Diseases (to C.F.B.), from the US National Institute of Eye Diseases (to D.W.S.) and from the US National Institute of Neurological Disorders and Stroke (to J.R.L.).
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Boerkoel, C., Takashima, H., John, J. et al. Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia. Nat Genet 30, 215–220 (2002). https://doi.org/10.1038/ng821
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DOI: https://doi.org/10.1038/ng821
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