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

✍ Scribed by Karin Buiting; Deniz Kanber; José I. Martín-Subero; Wolfgang Lieb; Paulien Terhal; Beate Albrecht; Sabine Purmann; Stephanie Gross; Christina Lich; Reiner Siebert; Bernhard Horsthemke; Gabriele Gillessen-Kaesbach


Publisher
John Wiley and Sons
Year
2008
Tongue
English
Weight
290 KB
Volume
29
Category
Article
ISSN
1059-7794

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✦ Synopsis


Communicated by Nancy B. Spinner

Maternal uniparental disomy 14 [upd( 14)mat] is associated with a recognizable phenotype that includes preand 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 À1 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. Hum Mutat 29(9),