title: Four novel cases of permanent neonatal diabetes mellitus caused by homozygous mutations in the glucokinase gene.
abstract: Permanent neonatal diabetes mellitus (PNDM) caused by homozygous mutations in the glucokinase gene (GCK) is rare and only eight homozygous GCK mutations have been reported so far. Heterozygous GCK mutations cause maturity-onset diabetes of the young (MODY). We report four patients with growth retardation from two separate families (with three siblings in one family and one patient in another family) presenting with persistent hyperglycaemia within the first two days of life. We found one homozygous non-sense mutation (Q98X) in GCK in three siblings from one family and a homozygous missense GCK mutation (G261R) in one patient from another family. Both mutations have been identified previously in GCK-MODY in the heterozygous state. However, this is the first study to report the homozygous forms of these mutations in PNDM. We report four novel cases of PNDM caused by homozygous GCK mutations, including a non-sense mutation in exon 3 (Q98X) and a missense mutation in exon 7 (G261R).
authors.affiliation: Institute of Child Health, University College London, Great Ormond Street Hospital for Children NHS Trust, London, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Bennett
authors.forename: Chela
authors.initials: C
authors.lastname: James
authors.forename: Angham
authors.initials: A
authors.lastname: Mutair
authors.forename: Hala
authors.initials: H
authors.lastname: Al-Shaikh
authors.forename: Aisha
authors.initials: A
authors.lastname: Sinani
authors.forename: Khalid
authors.initials: K
authors.lastname: Hussain
mesh_terms: D018389:Codon, Nonsense; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005941:Glucokinase / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D035781:Siblings
chemical_list: D018389:Codon, Nonsense; D005941:Glucokinase