Clinical characterisation of the multiple maternal hypomethylation syndrome in siblings

European Journal of Human Genetics : EJHG
Susanne E BoonenJohanne M D Hahnemann

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.

References

Nov 24, 2001·Science·D Bourc'hisT H Bestor
Apr 5, 2002·Nature·Hannah JudsonDavid T Bonthron
Dec 10, 2002·Journal of Medical Genetics·I K Temple, J P H Shield
Sep 8, 2004·Analytical Biochemistry·Jean-Michel DupontIvo Glynne Gut
Jul 5, 2005·Human Reproduction Update·Bernhard Horsthemke, Michael Ludwig
Mar 15, 2006·Nature Reviews. Genetics·Eric J Richards
Mar 17, 2006·Human Reproduction Update·I B Van den Veyver, T K Al-Hussaini
May 26, 2006·Orphanet Journal of Rare Diseases·Melanie EhrlichCorry Weemaes

❮ Previous
Next ❯

Citations

Oct 6, 2010·Reviews in Endocrine & Metabolic Disorders·I Karen Temple, Julian P H Shield
May 31, 2013·Journal of Human Genetics·Hidenobu Soejima, Ken Higashimoto
Jun 8, 2012·Molekuliarnaia biologiia·E A SazhenovaI N Lebedev
Apr 12, 2014·Journal of Medical Genetics·Almuth CaliebeReiner Siebert
Aug 31, 2010·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Deborah J G Mackay, I Karen Temple
May 23, 2012·American Journal of Medical Genetics. Part a·Karen Y NiederhofferCornelius F Boerkoel
Sep 17, 2013·American Journal of Medical Genetics. Part a·Guido CocchiAndrea Riccio
Jan 13, 2015·Biomolecular Concepts·Deborah J G MackayGuiomar Perez de Nanclares
May 29, 2016·Trends in Genetics : TIG·Marta Sanchez-DelgadoDavid Monk
May 26, 2016·Birth Defects Research. Part A, Clinical and Molecular Teratology·Julia KolarovaReiner Siebert
Apr 12, 2012·The Journal of Clinical Endocrinology and Metabolism·Gustavo Perez-NanclaresUNKNOWN Spanish PHP Group
Aug 3, 2017·Neonatal Network : NN·Martha Anne ZammitJean Calleja-Agius
Mar 2, 2018·Environmental Epigenetics·Adelheid SoubryHeather M Stapleton
Feb 19, 2020·Human Reproduction Update·Miriam ElbrachtThomas Eggermann
Oct 27, 2020·Frontiers in Genetics·Chiara PapulinoLucia Altucci
Apr 4, 2021·International Journal of Molecular Sciences·Laura FontanaMonica Miozzo
May 23, 2021·Immunology·Jessica CarriereChristian Stehlik

❮ Previous
Next ❯

Related Concepts

Related Feeds

Beckwith-Wiedemann syndrome

Beckwith-Wiedemann syndrome is an imprinting disorder characterized by overgrowth, congenital malformations and predisposition to tumors. Discover the latest research on Beckwith-Wiedemann Syndrome here.