title: [Two novel EIF2AK3 mutations in a Chinese boy with Wolcott-Rallison syndrome].
abstract: OBJECTIVE
  Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disorder characterized by the association of permanent neonatal or early-infancy insulin-dependent diabetes, multiple epiphyseal dysplasia and growth retardation, and other variable multisystem clinical manifestations. Here we describe a Chinese boy affected by WRS. Genetic testing of his EIF2AK3 gene was performed in order to elucidate molecular variations and subsequently to provide credible genetic counseling for prenatal diagnosis in his family.
  
  
  METHODS
  Based on analysis of a nine-year-old boy's clinical symptoms associated with biochemical examination and imaging, the diagnosis of WRS was therefore made. Genomic DNAs were extracted from peripheral blood leukocytes from the boy and his parents with their informed consent for genetic studies. All EIF2AK3 exons and intron-exon boundaries were amplified by Touch-down polymerase chain reaction (Touch-down PCR) and sequenced.
  
  
  RESULTS
  Direct sequencing of PCR products revealed the presence of a heterozygous T insertion (c.1408_1409insT) in exon 8 of the EIF2AK3 gene leading to frameshifting and termination, and another heterozygous T to A exchange (c.1596T > A) in exon 9 of the EIF2AK3 gene resulting in nonsense C532X mutation.
  
  
  CONCLUSIONS
  Combining mutation screening of EIF2AK3 gene with clinical manifestations and effective examination may provide a reliable diagnostic method for patients. In this research, two novel mutations identified in the Chinese boy locate in the catalytic domain of the EIF2AK3 gene, disrupting the ability of autophosphorylation, leading to the truncated proteins that are unable to phosphorylate the natural substrate, which are responsible for the phenotype of Wolcott-Rallison syndrome.
authors.affiliation: Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, WHO Collaborating Project for Community Control of Hereditary Diseases, Beijing 100005, China.
authors.forename: Dai-Rong
authors.initials: DR
authors.lastname: Feng
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
authors.forename: Shi-Min
authors.initials: SM
authors.lastname: Zhao
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Shi
authors.forename: Wei-Chen
authors.initials: WC
authors.lastname: Wang
authors.forename: Shang-Zhi
authors.initials: SZ
authors.lastname: Huang
mesh_terms: D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D004838:Epiphyses / Q000002:abnormalities; D006801:Humans; D008297:Male; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics*; D019892:eIF-2 Kinase / Q000235:genetics*
chemical_list: C460640:EIF2AK3 protein, human; D019892:eIF-2 Kinase