Relative frequency of underlying genetic causes for the development of UPD(14)pat-like phenotype.
Relative frequency of underlying genetic causes for the development of UPD(14)pat-like phenotype.
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DOI：
10.1038/ejhg.2012.26
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发表时间：
2012-09
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--
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父本单亲二体14（UPD（14）pat）导致独特的临床特征群，并且类似的表型群也由涉及DLK 1-MEG 3基因间差异甲基化区域（IG-DMR）和/或MEG 3-DMR的微缺失以及影响DMR的表位突变（高甲基化）引起。然而，这些潜在遗传原因的相对频率仍有待澄清，以及UPD（14）pat的潜在机制，即三体拯救（TR），配子互补（GC），单体拯救（MR）和受精后有丝分裂错误（PE）。为了验证这一点，我们对26例UPD（14）Pat样表型患者依次进行了甲基化分析、微卫星分析、荧光原位杂交和基于阵列的比较基因组杂交。因此，我们在17名患者（65.4%）中发现了UPD（14）pat，在5名患者（19.2%）中发现了不同模式的微缺失，在4名患者（15.4%）中发现了表位突变。此外，发现5例（29.4%）患者通过TR或GC产生UPD（14）pat，11例（64.7%）患者通过MR或PE产生，1例（5.9%）患者通过PE产生。分娩时高龄产妇（≥35岁）主要见于MR/PE亚型。这些结果表明，UPD（14）pat样表型发生的潜在遗传原因的相对频率与其他印记疾病不同，并且分娩时的高龄作为通过减数分裂1不分离产生缺体卵母细胞的易感因素可能参与MR介导的UPD（14）pat的发生。
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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DOI：
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发表时间：
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影响因子：
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发表时间：
2002-07-01
期刊：
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