DNA hypomethylation, transient neonatal diabetes, and prune belly sequence in one of two identical twins.
One known genetic mechanism for transient neonatal diabetes is loss of methylation at 6q24. The etiology of prune belly sequence is unknown but a genetic defect, affecting the mesoderm from which the triad abdominal muscle hypoplasia, urinary tract abnormalities, and cryptorchidism develop, has been suggested. We investigated a family, including one twin, with transient neonatal diabetes and prune belly sequence. Autoantibody tests excluded type 1 diabetes. Microsatellite marker analysis confirmed the twins being monozygotic. We identified no mutations in ZFP57, KCNJ11, ABCC8, GCK, HNF1A, HNF1B, HNF3B, IPF1, PAX4, or ZIC3. The proband had loss of methylation at the 6q24 locus TNDM and also at the loci IGF2R, DIRAS3, and PEG1, while the other family members, including the healthy monozygotic twin, had normal findings. The loss of methylation on chromosome 6q24 and elsewhere may indicate a generalized maternal hypomethylation syndrome, which accounts for both transient neonatal diabetes and prune belly sequence.
Laborie
Lene Bjerke
LB
Department of Pediatrics, Haukeland University Hospital, 5021 Bergen, Norway.
Mackay
Deborah J G
DJ
Temple
I Karen
IK
Molven
Anders
A
Søvik
Oddmund
O
Njølstad
Pål Rasmus
PR
D002896:Chromosomes, Human, Pair 6; D004247:DNA / Q000235:genetics*; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D003920:Diabetes Mellitus / Q000097:blood / Q000235:genetics*; D004200:Diseases in Twins / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D014430:Twins, Monozygotic
D005819:Genetic Markers; D004247:DNA