Clinical features of maternal uniparental disomy 14 in patients with an epimutation and a deletion of the imprinted DLK1/GTL2 gene cluster

被引：52

作者：

Buiting, Karin ^{[1
]}

Kanber, Deniz ^{[1
]}

Martin-Subero, Jose I. ^{[2
]}

Lieb, Wolfgang ^{[3
]}

Terhal, Paulien ^{[4
]}

Albrecht, Beate ^{[1
]}

Purmann, Sabine ^{[3
]}

Gross, Stephanie ^{[1
]}

Lich, Christina ^{[1
]}

Siebert, Reiner ^{[2
]}

Horsthernke, Bernhard ^{[1
]}

Gillessen-Kaesbach, Gabriele ^{[3
]}

机构：

[1] Univ Klinikum Essen, Inst Humangenet, D-45122 Essen, Germany

[2] Univ Klinikum Schleswig Holstein, Inst Humangenet, Kiel, Germany

[3] Med Univ Lubeck, Inst Humangenet, D-23538 Lubeck, Germany

[4] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands

来源：

HUMAN MUTATION | 2008年 / 29卷 / 09期

关键词：

imprinting defect; uniparental disomy; epimutation; microdeletion; DLK1; GTL2;

D O I：

10.1002/humu.20771

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Maternal uniparental disomy 14 [upd(14)mat] is associated with a recognizable phenotype that includes pre- and postnatal growth retardation, neonatal hypotonia, feeding problems and precocious puberty. Chromosome 14 contains an imprinted gene cluster, which is regulated by a differentially methylated region (IG-DMR) between DLK1 and GTL2. Here we report on four patients with clinical features of upd(14)mat who show a maternal-only methylation pattern, but biparental inheritance for chromosome 14. In three of the patients loss of paternal methylation appears to be a primary epimutation, whereas the other patient has a paternally derived deletion of -1 Mb that includes the imprinted DLK1-GTL2 gene cluster. These findings demonstrate that the upd(14)mat phenotype is caused by altered expression of genes within this cluster.

引用

页码：1141 / 1146

页数：6

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