title: Novel homozygous likely-pathogenic intronic variant in INS causing permanent neonatal diabetes in siblings.
abstract: Permanent neonatal diabetes (PNDM) is a rare genetic condition characterized by hyperglycemia, insulinopenia, and failure to thrive beginning in the first 6 months of life. Recessive mutations in INS lead to decreased production of insulin via a variety of mechanisms. We present a case of two brothers, born to consanguineous parents, with a novel homozygous intronic variant in the INS gene. Each patient presented with intrauterine growth restriction (IUGR) and significant hyperglycemia within the first 24 h of life. All the grandparents have a diagnosis of diabetes, one of them requiring insulin treatment and the parents currently deny personal histories of diabetes. Although this mutation has not previously been described, given the segregation of the mutation, absence of heterozygosity (AOH) in the genomic region encompassing the INS locus, documented insulinopenia, and high neonatal insulin requirements, we suspect that this variant is pathogenic. Possible implications for personalized treatment of the underlying molecular etiology for an individual's diabetes are discussed.
authors.forename: Rachel
authors.initials: R
authors.lastname: Courtney
authors.forename: Candace
authors.initials: C
authors.lastname: Gamble
authors.forename: Monica L
authors.initials: ML
authors.lastname: Arango
authors.forename: Avni
authors.initials: A
authors.lastname: Shah
authors.forename: Nunilo I
authors.initials: NI
authors.lastname: Rubio
authors.forename: Joanne
authors.initials: J
authors.lastname: Nguyen
authors.forename: David
authors.initials: D
authors.lastname: Rodriguez-Buritica
mesh_terms: D000328:Adult; D003241:Consanguinity; D003920:Diabetes Mellitus / Q000209:etiology*; D005260:Female; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D007328:Insulin / Q000235:genetics*; D007438:Introns / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011379:Prognosis; D035781:Siblings
chemical_list: D007328:Insulin