title: Organisation of the human PAX4 gene and its exclusion as a candidate for the Wolcott-Rallison syndrome.
abstract: Neonatal diabetes mellitus is a rare condition, the causes of which are mostly unknown. One well defined though very rare entity is the autosomal recessive Wolcott-Rallison syndrome, in which permanent neonatal diabetes, osteopenia, and epiphyseal dysplasia occur. Only five previous families have been reported, and here we describe the second in which parental consanguinity was present. The proband was born to first cousin parents and died at 2 years from the sequelae of poorly controlled diabetes. To test the hypothesis that mutation of PAX4, required in the mouse for pancreatic islet beta cell development, might cause WRS, the structure of the human PAX4 gene was deduced and DNA from two unrelated WRS patients sequenced. No PAX4 mutation was present, though the entire coding region was sequenced in both patients. It therefore appears unlikely that PAX4 is involved in the aetiology of Wolcott-Rallison syndrome, though it remains a good candidate for other forms of neonatal diabetes mellitus.
authors.affiliation: University of Edinburgh, Molecular Medicine Centre, Western General Hospital, UK.
authors.forename: D T
authors.initials: DT
authors.lastname: Bonthron
authors.forename: N
authors.initials: N
authors.lastname: Dunlop
authors.forename: D G
authors.initials: DG
authors.lastname: Barr
authors.forename: A A
authors.initials: AA
authors.lastname: El Sanousi
authors.forename: L I
authors.initials: LI
authors.lastname: Al-Gazali
mesh_terms: D000015:Abnormalities, Multiple / Q000000981:diagnostic imaging / Q000235:genetics*; D000595:Amino Acid Sequence; D003922:Diabetes Mellitus, Type 1 / Q000000981:diagnostic imaging / Q000235:genetics*; D004838:Epiphyses / Q000002:abnormalities*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D051761:Paired Box Transcription Factors; D011859:Radiography; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C491709:PAX4 protein, human; D051761:Paired Box Transcription Factors; D014157:Transcription Factors