title: Two novel mutations in the EIF2AK3 gene in children with Wolcott-Rallison syndrome.
abstract: Wolcott-Rallison syndrome (WRS, OMIM 226980) is a rare autosomal recessive disorder characterized by permanent neonatal diabetes mellitus, epiphyseal dysplasia, and other multisystemic clinical manifestations. We described two novel mutations in the EIF2AK3 gene in two consanguineous families with WRS from Brazil and Morocco. We have observed in case 1 a homozygous C > T replacement at base pair c.1192 at exon 7, generating a stop codon at position 398 (Gln398Stop). Both of his parents were found to be heterozygous for the mutation. We detected in both parents of case 2, a deceased Moroccan girl, a duplication of base pair c.851A at exon 5 (c.851dupA) leading to a frameshift and a stop codon at position 285 (p.Pro285AlafsX3). Both cases 1 and 2 had neonatal diabetes mellitus, multiple epiphyseal dysplasia, and growth delay, and presented episodes of acute hepatic dysfunction. Case 1 presented central hypothyroidism, developmental delay, and mild mental retardation. Case 2 presented a fatal episode of acute renal failure. The clinical phenotype associated with the syndrome can be variable, but a combination of infancy-onset diabetes mellitus, multiple epiphyseal dysplasia, and hepatic and/or renal dysfunction is the mainstay of diagnosis.
authors.affiliation: Endocrinology Unit, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: André F
authors.initials: AF
authors.lastname: Reis
authors.forename: Caroline
authors.initials: C
authors.lastname: Kannengiesser
authors.forename: Farida
authors.initials: F
authors.lastname: Jennane
authors.forename: Thais Della
authors.initials: TD
authors.lastname: Manna
authors.forename: Nadir
authors.initials: N
authors.lastname: Cheurfa
authors.forename: Claire
authors.initials: C
authors.lastname: Oudin
authors.forename: Roberta Diaz
authors.initials: RD
authors.lastname: Savoldelli
authors.forename: Carolina
authors.initials: C
authors.lastname: Oliveira
authors.forename: Bernard
authors.initials: B
authors.lastname: Grandchamp
authors.forename: Fernando
authors.initials: F
authors.lastname: Kok
authors.forename: Gilberto
authors.initials: G
authors.lastname: Velho
mesh_terms: D001938:Brazil; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D004838:Epiphyses / Q000002:abnormalities; D005192:Family Health; D017809:Fatal Outcome; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D009018:Morocco; D010009:Osteochondrodysplasias / Q000235:genetics; D017354:Point Mutation; D019892:eIF-2 Kinase / Q000235:genetics*
chemical_list: C460640:EIF2AK3 protein, human; D019892:eIF-2 Kinase