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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
Author(s) -
Buiting Karin,
Kanber Deniz,
MartínSubero José I.,
Lieb Wolfgang,
Terhal Paulien,
Albrecht Beate,
Purmann Sabine,
Gross Stephanie,
Lich Christina,
Siebert Reiner,
Horsthemke Bernhard,
GillessenKaesbach Gabriele
Publication year - 2008
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20771
Subject(s) - genomic imprinting , biology , uniparental disomy , imprinting (psychology) , genetics , phenotype , gene cluster , hypotonia , gene , methylation , chromosome , dna methylation , karyotype , gene expression
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. Hum Mutat 0, 1–6, 2008. © 2008 Wiley‐Liss, Inc.