%0 Journal Article
%T Potential pathogenetic role of a novel ABCC8 missense variant on both transient neonatal diabetes mellitus and fetal growth restriction: a case report.
%A Perri A
%A Fattore S
%A Minucci A
%A Rinelli M
%A Barbetti F
%A Pitocco D
%A Costa S
%A Vento G
%J Mol Biol Rep
%V 51
%N 1
%D 2024 Jun 14
%M 38874636
%F 2.742
%R 10.1007/s11033-024-09668-2
%X <B>BACKGROUND: </B>The diagnosis of neonatal diabetes can be problematic in preterm infants with fetal growth restriction (FGR). Growth restricted fetuses may have impaired insulin production and secretion; low birthweight infants may have a reduced response to insulin. We report a novel missense ABCC8 variant associated with a clinical phenotype compatible with transient neonatal diabetes mellitus (TNDM) in a fetal growth restricted preterm infant.<BR><B>RESULTS: </B>A preterm growth restricted infant experienced hyperglycemia from the first day of life, requiring insulin therapy on the 13th and 15th day of life and leading to the diagnosis of TNDM. Glycemic values normalized from the 35th day of life onwards. Genetic screening was performed by next generation sequencing, using a Clinical Exon panel of 4800 genes, filtered for those associated with the clinical presentation and by means of methylation-specific multiplex ligation-dependent probe amplification analysis to identify chromosomal aberrations at 6q24. Genetic tests excluded defects at 6q24 and were negative for KCNJ11, SLC2A2 (GLUT-2) and HNF1B, but revealed the presence of the heterozygous missense variant c.2959T > C (p.Ser987Pro) in ABCC8 gene. The presence of the variant was excluded in parents' DNA and the proband variant was then considered de novo.<BR><B>CONCLUSIONS: </B>In our infant, the persistence of hyperglycemia beyond 3 weeks of life led us to the diagnosis of TNDM and to hypothesize a possible genetic cause. The genetic variant we found could be, most likely, the main cause of both FGR and TNDM.