title: Permanent neonatal diabetes caused by creation of an ectopic splice site within the INS gene.
abstract: BACKGROUND
  The aim of this study was to characterize the genetic etiology in a patient who presented with permanent neonatal diabetes at 2 months of age.
  
  
  RESULTS
  Regulatory elements and coding exons 2 and 3 of the INS gene were amplified and sequenced from genomic and complementary DNA samples. A novel heterozygous INS mutation within the terminal intron of the gene was identified in the proband and her affected father. This mutation introduces an ectopic splice site leading to the insertion of 29 nucleotides from the intronic sequence into the mature mRNA, which results in a longer and abnormal transcript.
  
  
  CONCLUSIONS
  This study highlights the importance of routinely sequencing the exon-intron boundaries and the need to carry out additional studies to confirm the pathogenicity of any identified intronic genetic variants.
authors.affiliation: Endocrinology and Diabetes Research Group, Hospital de Cruces, Universitat Politècnica de València/Euskal Herriko Unibertsitateko, Barakaldo, Bizkaia, Spain.
authors.forename: Intza
authors.initials: I
authors.lastname: Garin
authors.forename: Guiomar
authors.initials: G
authors.lastname: Perez de Nanclares
authors.forename: Elena
authors.initials: E
authors.lastname: Gastaldo
authors.forename: Lorna W
authors.initials: LW
authors.lastname: Harries
authors.forename: Oscar
authors.initials: O
authors.lastname: Rubio-Cabezas
authors.forename: Luis
authors.initials: L
authors.lastname: Castaño
mesh_terms: D001483:Base Sequence; D002648:Child; D003920:Diabetes Mellitus / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007328:Insulin / Q000737:chemistry / Q000235:genetics*; D007438:Introns / Q000235:genetics; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D011247:Pregnancy; D011384:Proinsulin / Q000737:chemistry / Q000235:genetics; D017434:Protein Structure, Tertiary; D022821:RNA Splice Sites / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D007328:Insulin; D022821:RNA Splice Sites; D012333:RNA, Messenger; D011384:Proinsulin