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.
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Acknowledgements
We thank the family for their collaboration. We thank the technicians at the Kennedy Center and Jonathan Callaway, Salisbury, for their laboratory work and photographer Jette B Rasmussen for excellent assistance with preparation of the figures. Deborah JG Mackay was funded by Diabetes UK.
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Boonen, S., Pörksen, S., Mackay, D. et al. Clinical characterisation of the multiple maternal hypomethylation syndrome in siblings. Eur J Hum Genet 16, 453–461 (2008). https://doi.org/10.1038/sj.ejhg.5201993
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DOI: https://doi.org/10.1038/sj.ejhg.5201993
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