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. 2012 Sep;20(9):928-32.
doi: 10.1038/ejhg.2012.26. Epub 2012 Feb 22.

Relative frequency of underlying genetic causes for the development of UPD(14)pat-like phenotype

Masayo Kagami  1 , Fumiko Kato, Keiko Matsubara, Tomoko Sato, Gen Nishimura, Tsutomu Ogata
Affiliations

Relative frequency of underlying genetic causes for the development of UPD(14)pat-like phenotype

Masayo Kagami et al. Eur J Hum Genet. 2012 Sep.

Abstract

Paternal uniparental disomy 14 (UPD(14)pat) results in a unique constellation of clinical features, and a similar phenotypic constellation is also caused by microdeletions involving the DLK1-MEG3 intergenic differentially methylated region (IG-DMR) and/or the MEG3-DMR and by epimutations (hypermethylations) affecting the DMRs. However, relative frequency of such underlying genetic causes remains to be clarified, as well as that of underlying mechanisms of UPD(14)pat, that is, trisomy rescue (TR), gamete complementation (GC), monosomy rescue (MR), and post-fertilization mitotic error (PE). To examine this matter, we sequentially performed methylation analysis, microsatellite analysis, fluorescence in situ hybridization, and array-based comparative genomic hybridization in 26 patients with UPD(14)pat-like phenotype. Consequently, we identified UPD(14)pat in 17 patients (65.4%), microdeletions of different patterns in 5 patients (19.2%), and epimutations in 4 patients (15.4%). Furthermore, UPD(14)pat was found to be generated through TR or GC in 5 patients (29.4%), MR or PE in 11 patients (64.7%), and PE in 1 patient (5.9%). Advanced maternal age at childbirth (≥35 years) was predominantly observed in the MR/PE subtype. The results imply that the relative frequency of underlying genetic causes for the development of UPD(14)pat-like phenotype is different from that of other imprinting disorders, and that advanced maternal age at childbirth as a predisposing factor for the generation of nullisomic oocytes through non-disjunction at meiosis 1 may be involved in the development of MR-mediated UPD(14)pat.

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Figures

Figure 1
Figure 1
Classification of 26 patients with UPD(14)pat-like phenotype.
Figure 2
Figure 2
The distribution of parental ages at childbirth according to the underlying genetic causes for the development of UPD(14)pat-like phenotype and UPD(14)pat subtypes. Of the five plots for the TR/GC subtype, open and black circles indicate the TR/GC subtype due to non-disjunction at paternal M1 and M2, respectively.
See this image and copyright information in PMC

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