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GENATLAS PHENOTYPE
last update : 19-05-2010
Symbol PNDM4
Location 11p15.5
Name permanent neonatal diabetes mellitus 4
Corresponding gene INS
Main clinical features
  • insulin-requiring hyperglycemia within the first 3 months of life, median age-at-diagnosis of diabetes is 9 weeks
  • diabetes usually presented with diabetic ketoacidosis or marked hyperglycemia (median plasma glucose at diagnosis was 681 mg/dl), not associated with cell autoantibodies and treated from diagnosis with insulin usually in replacement doses
    • Genetic determination autosomal dominant
    autosomal recessive
    Function/system disorder endocrinology
    Type disease
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    various types     mutations are in critical regions of the preproinsulin molecule, and prevent normal folding and progression of proinsulin in the insulin secretory pathway
    Remark(s)
  • recessively acting mutations reduce insulin synthesis and thus represent a unique pathogenic mechanism for human diabetes ( provide genetic evidence for the essential role of distinct nucleotide sequences in the regulation of the preproinsulin gene) (Garin 2010)
  • mutant proinsulin proteins associated with neonatal diabetes are retained in the endoplasmic reticulum and not efficiently secreted (Park 2010)
    • Genotype/Phenotype correlations
  • neonatal diabetes resulting from recessive INS mutations had a markedly different phenotype, with lower birth weight and an earlier age of diagnosis (Garin 2010)