ABCC8 gene mutations with different inheritance patterns have been well described to cause transient and permanent forms of neonatal diabetes with onset of hyperglycemia commonly before the age of 6 months, and rare cases between 6 and 12 months. However, recent analyses have also demonstrated ABCC8 gene mutations in patients with monogenic diabetes (maturity onset diabetes of the young, MODY), with milder clinical phenotypes and later onset of hyperglycemia. We report two siblings with diabetes mellitus due to a novel homozygous p.(Phe1068Ile) (c.3202T>A) missense mutation of the ABCC8 gene, but significantly different phenotypes. The index case was diagnosed with diabetes due to an incidental finding of hyperglycemia at the age of 3 years, while her younger sibling presented with severe hyperglycemia and hyperosmolar dehydration at the age of 10 weeks. The possibility of a significant discordance in the correlation between genotype and phenotype needs to be taken into account when ABCC8 mutation dependent diabetes occurs within the same family. Genetic screening in children with diabetes from consanguineous family needs consideration, especially in case of negative autoantibodies and early onset of hyperglycemia.

Cattoni, A., Jackson, C., Bain, M., Houghton, J., Wei, C. (2019). Phenotypic variability in two siblings with monogenic diabetes due to the same ABCC8 gene mutation. PEDIATRIC DIABETES, 20(4), 482-485 [10.1111/pedi.12826].

Phenotypic variability in two siblings with monogenic diabetes due to the same ABCC8 gene mutation

Cattoni A.;
2019

Abstract

ABCC8 gene mutations with different inheritance patterns have been well described to cause transient and permanent forms of neonatal diabetes with onset of hyperglycemia commonly before the age of 6 months, and rare cases between 6 and 12 months. However, recent analyses have also demonstrated ABCC8 gene mutations in patients with monogenic diabetes (maturity onset diabetes of the young, MODY), with milder clinical phenotypes and later onset of hyperglycemia. We report two siblings with diabetes mellitus due to a novel homozygous p.(Phe1068Ile) (c.3202T>A) missense mutation of the ABCC8 gene, but significantly different phenotypes. The index case was diagnosed with diabetes due to an incidental finding of hyperglycemia at the age of 3 years, while her younger sibling presented with severe hyperglycemia and hyperosmolar dehydration at the age of 10 weeks. The possibility of a significant discordance in the correlation between genotype and phenotype needs to be taken into account when ABCC8 mutation dependent diabetes occurs within the same family. Genetic screening in children with diabetes from consanguineous family needs consideration, especially in case of negative autoantibodies and early onset of hyperglycemia.
Articolo in rivista - Articolo scientifico
diabetes mellitus; infant; monogenic diabetes; siblings; sulfonylurea receptors; Adult; Child, Preschool; Consanguinity; Diabetes Mellitus, Type 2; Female; Humans; Infant; Male; Pakistan; Pedigree; Phenotype; Sulfonylurea Receptors; Biological Variation, Population; Mutation, Missense; Siblings
English
2019
20
4
482
485
reserved
Cattoni, A., Jackson, C., Bain, M., Houghton, J., Wei, C. (2019). Phenotypic variability in two siblings with monogenic diabetes due to the same ABCC8 gene mutation. PEDIATRIC DIABETES, 20(4), 482-485 [10.1111/pedi.12826].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/295467
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