title: Novel compound mutations of SMARCAL1 associated with severe Schimke immuno-osseous dysplasia in a Chinese patient.
abstract: BACKGROUND
  Schimke immuno-osseous dysplasia (SIOD) is a rare autosomal recessive pleiotropic disease caused by mutations in the SMARCAL1 gene. To date there have been no data from the Chinese population. Here, we report the first SIOD case in the Chinese population. No case with gross carpal bone age retardation has been reported previously.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Paediatrics, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, PR China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Yue
authors.forename: Shiyi
authors.initials: S
authors.lastname: Xiong
authors.forename: Liangzhong
authors.initials: L
authors.lastname: Sun
authors.forename: Weijun
authors.initials: W
authors.lastname: Huang
authors.forename: Ying
authors.initials: Y
authors.lastname: Mo
authors.forename: Liuyi
authors.initials: L
authors.lastname: Huang
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Jiang
authors.forename: Shumei
authors.initials: S
authors.lastname: Chen
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.forename: Yiming
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D002648:Child; D019295:Computational Biology; D004265:DNA Helicases / Q000737:chemistry / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics*
chemical_list: C412482:SMARCAL1 protein, human; D004265:DNA Helicases