Epimutation of the TNDM locus and the Beckwith-Wiedemann syndrome centromeric locus in individuals with transient neonatal diabetes mellitus.
Transient neonatal diabetes mellitus (TNDM) is characterised by intra-uterine growth retardation, while Beckwith-Wiedemann syndrome (BWS) is a clinically heterogeneous overgrowth syndrome. Both TNDM and BWS may be caused by aberrant loss of methylation (LOM) at imprinted loci on chromosomes 6q24 and 11p15.5 respectively. Here we describe two patients with a clinical diagnosis of TNDM caused by LOM at the maternally methylated imprinted domain on 6q24; in addition, these patients had LOM at the centromeric differentially methylated region of 11p15.5. This shows that imprinting anomalies can affect more than one imprinted locus and may alter the clinical presentation of imprinted disease.
Mackay
D J G
DJ
Wessex Regional Genetics Laboratory, Salisbury District Hospital, SP2 8BJ Salisbury, UK. djgm@soton.ac.uk
Hahnemann
J M D
JM
Boonen
S E
SE
Poerksen
S
S
Bunyan
D J
DJ
White
H E
HE
Durston
V J
VJ
Thomas
N S
NS
Robinson
D O
DO
Shield
J P H
JP
Clayton-Smith
J
J
Temple
I K
IK
D001506:Beckwith-Wiedemann Syndrome / Q000235:genetics* / Q000473:pathology; D001724:Birth Weight / Q000235:genetics; D002503:Centromere / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11; D002896:Chromosomes, Human, Pair 6; D019175:DNA Methylation; D003920:Diabetes Mellitus / Q000235:genetics* / Q000473:pathology; D044127:Epigenesis, Genetic; D018392:Genomic Imprinting; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn