TY - JOUR
T1 - Clinical characterisation of the multiple maternal hypomethylation syndrome in siblings
AU - Boonen, Susanne E
AU - Pörksen, Sven
AU - Mackay, Deborah Jg
AU - Oestergaard, Elsebet
AU - Olsen, Birthe
AU - Brøndum-Nielsen, Karen
AU - Temple, I Karen
AU - Hahnemann, Johanne Md
N1 - Keywords: Beckwith-Wiedemann Syndrome; Child, Preschool; Consanguinity; DNA Methylation; Diabetes Mellitus; Fatal Outcome; Female; Genomic Imprinting; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Male; Mothers; Pedigree; Phenotype; Siblings; Syndrome
PY - 2008
Y1 - 2008
N2 - We present the first clinical report of sibs with the multiple maternal hypomethylation syndrome. Both sisters presented with transient neonatal diabetes mellitus (TNDM). By methylation-specific PCR of bisulphite-treated DNA, we found a mosaic spectrum of hypomethylation at the following maternally methylated loci in both sibs: ZAC (6q24), KCNQ1OT1 (11p15.5), GRB10 (7p11.2-12), PEG3 (19q13), PEG1/MEST (7q32), and NESPAS (20q13). While the older sister has a milder phenotype, the younger one was severely ill and died at 11 months of age. Despite phenotypic differences, the sisters had several manifestations of both TNDM and BWS in common. The family is highly consanguineous, and the parents are first cousins. We suggest that the genetic defect in this family is a novel, most likely autosomal recessive defect of methylation mechanisms, either in the sisters or in their mother, affecting her oocyte imprinting. The recurrence with affected sibs as reported in this family has implications for genetic counselling.
AB - We present the first clinical report of sibs with the multiple maternal hypomethylation syndrome. Both sisters presented with transient neonatal diabetes mellitus (TNDM). By methylation-specific PCR of bisulphite-treated DNA, we found a mosaic spectrum of hypomethylation at the following maternally methylated loci in both sibs: ZAC (6q24), KCNQ1OT1 (11p15.5), GRB10 (7p11.2-12), PEG3 (19q13), PEG1/MEST (7q32), and NESPAS (20q13). While the older sister has a milder phenotype, the younger one was severely ill and died at 11 months of age. Despite phenotypic differences, the sisters had several manifestations of both TNDM and BWS in common. The family is highly consanguineous, and the parents are first cousins. We suggest that the genetic defect in this family is a novel, most likely autosomal recessive defect of methylation mechanisms, either in the sisters or in their mother, affecting her oocyte imprinting. The recurrence with affected sibs as reported in this family has implications for genetic counselling.
U2 - 10.1038/sj.ejhg.5201993
DO - 10.1038/sj.ejhg.5201993
M3 - Journal article
C2 - 18197189
SN - 1018-4813
VL - 16
SP - 453
EP - 461
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 4
ER -
