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Clinical characterisation of the multiple maternal hypomethylation syndrome in siblings

Clinical characterisation of the multiple maternal hypomethylation syndrome in siblings
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.
male, mothers, infant, parents, pedigree, dna methylation, family, diseases, diabetes, beckwith-wiedemann syndrome, phenotype, child, fatal outcome, research, genomic imprinting, recurrence, dna, syndrome, humans, consanguinity, newborn, female, diabetes mellitus, preschool, siblings, research support, genetics, report
1018-4813
453-461
Boonen, S.E.
d1c63e8f-4d38-4ff3-a6fd-f29db9a05e3b
Porksen, S.
903a0431-23f5-4b7f-a989-4120a7d5ecc9
Mackay, D.J.
588a653e-9785-4a00-be71-4e547850ee4a
Oestergaard, E.
d27ddfd2-ce4d-433c-8fd4-fb1e5da713a3
Olsen, B.
9fb18f61-9b54-4f5e-98f8-75163aaa5881
Brondum-Nielsen, K.
be6e5fa5-6fcc-4c3b-97c9-4f0871976cbf
Temple, I.K.
d63e7c66-9fb0-46c8-855d-ee2607e6c226
Hahnemann, J.M.
567cb866-246c-4b6f-8a81-c65a215931d2
Boonen, S.E.
d1c63e8f-4d38-4ff3-a6fd-f29db9a05e3b
Porksen, S.
903a0431-23f5-4b7f-a989-4120a7d5ecc9
Mackay, D.J.
588a653e-9785-4a00-be71-4e547850ee4a
Oestergaard, E.
d27ddfd2-ce4d-433c-8fd4-fb1e5da713a3
Olsen, B.
9fb18f61-9b54-4f5e-98f8-75163aaa5881
Brondum-Nielsen, K.
be6e5fa5-6fcc-4c3b-97c9-4f0871976cbf
Temple, I.K.
d63e7c66-9fb0-46c8-855d-ee2607e6c226
Hahnemann, J.M.
567cb866-246c-4b6f-8a81-c65a215931d2

Boonen, S.E., Porksen, S., Mackay, D.J., Oestergaard, E., Olsen, B., Brondum-Nielsen, K., Temple, I.K. and Hahnemann, J.M. (2008) Clinical characterisation of the multiple maternal hypomethylation syndrome in siblings. European Journal of Human Genetics, 16 (4), 453-461. (doi:10.1038/sj.ejhg.5201993).

Record type: Article

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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More information

Published date: 2008
Keywords: male, mothers, infant, parents, pedigree, dna methylation, family, diseases, diabetes, beckwith-wiedemann syndrome, phenotype, child, fatal outcome, research, genomic imprinting, recurrence, dna, syndrome, humans, consanguinity, newborn, female, diabetes mellitus, preschool, siblings, research support, genetics, report

Identifiers

Local EPrints ID: 59513
URI: http://eprints.soton.ac.uk/id/eprint/59513
ISSN: 1018-4813
PURE UUID: b7bdc908-9819-4792-8429-9884dc4900e4
ORCID for D.J. Mackay: ORCID iD orcid.org/0000-0003-3088-4401
ORCID for I.K. Temple: ORCID iD orcid.org/0000-0002-6045-1781

Catalogue record

Date deposited: 03 Sep 2008
Last modified: 16 Mar 2024 03:05

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Contributors

Author: S.E. Boonen
Author: S. Porksen
Author: D.J. Mackay ORCID iD
Author: E. Oestergaard
Author: B. Olsen
Author: K. Brondum-Nielsen
Author: I.K. Temple ORCID iD
Author: J.M. Hahnemann

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