Novel compound mutations of SMARCAL1 associated with severe Schimke immuno-osseous dysplasia in a Chinese patient

Methods. The index patient was diagnosed by clinical and laboratory investigations. Mutations analysis of the SMARCAL1 gene and haplotype analysis were performed in the family. Structural predictions of the wild-type and mutant proteins were conducted. Results. Severe SIOD was diagnosed in an 8-year-old boy, who exhibited growth failure, recurrent infection, neutropaenia, spondyloepiphyseal dysplasia, focal segmental glomerulosclerosis, T cell immunodeficiency and facial dysmorphism. Marked carpal bone age retardation was also observed. Sequence analysis of the SMARCAL1 gene revealed two novel mutations: c.3G > A (p.Met1?) and c.1682G > A (p.Arg561His) in the boy. Haplotype analysis and mutation detection showed that the father is the carrier of c.3G > A (p.Met1?) and the mother is the carrier of c.1682G > A (p.Arg561His). The paternal mutation, c.3G > A (p.Met1?), is predicted to introduce a new open reading frame, resulting in truncation of 103 amino acids at the N-terminus. The maternal mutation occurred in the SNF2-related domain involved in ATP hydrolyzation and DNA binding and is predicted to alter the local spatial structure of the protein. Conclusion. We report the first SIOD patient from China, who exhibited gross carpal bone age retardation and carried two novel mutations, c.3G > A (p.Met1?) and c.1682G > A (p.Arg561His), in the SMARCAL1 gene.