Clinical characterisation of the multiple maternal hypomethylation syndrome in siblings.
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.
Boonen
Susanne E
SE
Genetic Counselling Clinic, Kennedy Center, Glostrup, Denmark.
Pörksen
Sven
S
Mackay
Deborah Jg
DJ
Oestergaard
Elsebet
E
Olsen
Birthe
B
Brondum-Nielsen
Karen
K
Temple
I Karen
IK
Hahnemann
Johanne Md
JM
D001506:Beckwith-Wiedemann Syndrome / Q000235:genetics; D002675:Child, Preschool; D003241:Consanguinity; D019175:DNA Methylation; D003920:Diabetes Mellitus / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000235:genetics*; D008297:Male; D009035:Mothers; D010375:Pedigree; D010641:Phenotype; D035781:Siblings; D013577:Syndrome