Clinical features of maternal uniparental disomy 14 in patients with an epimutation and a deletion of the imprinted DLK1/GTL2 gene cluster.
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.
Buiting
Karin
K
Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany. karin.buiting@uni-due.de
Kanber
Deniz
D
Martín-Subero
José I
JI
Lieb
Wolfgang
W
Terhal
Paulien
P
Albrecht
Beate
B
Purmann
Sabine
S
Gross
Stephanie
S
Lich
Christina
C
Siebert
Reiner
R
Horsthemke
Bernhard
B
Gillessen-Kaesbach
Gabriele
G
D000328:Adult; D002135:Calcium-Binding Proteins; D002648:Child; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D044127:Epigenesis, Genetic; D005260:Female; D017353:Gene Deletion; D018392:Genomic Imprinting; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009035:Mothers; D005810:Multigene Family; D009154:Mutation; D011506:Proteins; D062085:RNA, Long Noncoding; D024182:Uniparental Disomy / Q000235:genetics* / Q000503:physiopathology
D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C498907:MEG3 non-coding RNA, human; D008565:Membrane Proteins; D011506:Proteins; D062085:RNA, Long Noncoding