title: Clinical characterisation of the multiple maternal hypomethylation syndrome in siblings.
abstract: 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.
authors.affiliation: Genetic Counselling Clinic, Kennedy Center, Glostrup, Denmark.
authors.forename: Susanne E
authors.initials: SE
authors.lastname: Boonen
authors.forename: Sven
authors.initials: S
authors.lastname: Pörksen
authors.forename: Deborah Jg
authors.initials: DJ
authors.lastname: Mackay
authors.forename: Elsebet
authors.initials: E
authors.lastname: Oestergaard
authors.forename: Birthe
authors.initials: B
authors.lastname: Olsen
authors.forename: Karen
authors.initials: K
authors.lastname: Brondum-Nielsen
authors.forename: I Karen
authors.initials: IK
authors.lastname: Temple
authors.forename: Johanne Md
authors.initials: JM
authors.lastname: Hahnemann
mesh_terms: 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