Clinical characterisation of the multiple maternal hypomethylation syndrome in siblings

被引：39

作者：

Boonen, Susanne E. ^{[1
]}

Poerksen, Sven ^{[2
]}

Mackay, Deborah J. G. ^{[3
,4
]}

Oestergaard, Elsebet ^{[5
,6
]}

Olsen, Birthe ^{[2
]}

Brondum-Nielsen, Karen ^{[1
]}

Temple, I. Karen ^{[3
,7
]}

Hahnemann, Johanne M. D. ^{[5
]}

机构：

[1] Kennady Ctr, Genet Counselling Clin, Glostrup, Denmark

[2] Glostup Univ Hosp, Dept Paediat, Glostrup, Denmark

[3] Univ Southampton, Div Human Genet, Southampton, Hants, England

[4] Salisbury Dist Hosp, Wessex Reg Genet Lab, Salisbury, Wilts, England

[5] Kennedy Ctr, Med Genet Lab, Glostrup, Denmark

[6] Rigs Hosp, Dept Clin Genet, Copenhagen, Denmark

[7] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England

来源：

EUROPEAN JOURNAL OF HUMAN GENETICS | 2008年 / 16卷 / 04期

关键词：

genomic imprinting; DNA methylation; Beckwith-Wiedemann syndrome; transient neonatal diabetes mellitus; multiple maternal hypomethylation syndrome;

D O I：

10.1038/sj.ejhg.5201993

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：453 / 461

页数：9

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