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 immunodeficiency. 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.