Temple Syndrome (TS14) is an imprinting disorder caused by molecular disruptions of the imprinted region in 14q32 (MEG3:TSS-DMR). The frequency of the three known TS14 subtypes (deletions, maternal uniparental disomy (upd(14)mat), loss of methylation (LOM)) is currently in discussion, and within the LOM group, the occurrence of Multilocus Imprinting Disturbances (MLID) has been identified. We present 16 TS14 patients with molecular alterations affecting the MEG3:TSS-DMR, comprising seven patients (43.8%) with LOM, six carriers with upd(14)mat (37.5%), and three cases (18.8%) with a deletion affecting the paternal MEG3:TSS-DMR. We did not find any evidence for MLID in the LOM group, including two cases in which different tissues were available. Whole exome sequencing (WES) in the MEG3:TSS-DMR LOM patients and their parents (Trio WES) did not reveal an obvious pathogenic variant which might cause aberrant methylation at imprinted loci. By summarizing our data with those from the literature, we could show that MLID affecting clinically relevant imprinted loci is rare in TS14 and therefore differs markedly from other imprinting disorders associated with MLID, e.g. Silver-Russell syndrome (SRS) and Beckwith-Wiedemann syndrome (BWS). However, consistent with the clinical overlap with TS14, in SRS patients carrying MLID the MEG3:TSS-DMR is frequently affected. Variants in the known candidate genes for maternal effect variants causing MLID and fetal MLID determinants could not be identified in TS14 patients. Thus, 14q32 epimutations probably have other molecular causes than epimutations in BWS or SRS patients.

庙宇综合症（TS14）是由14q32（MEG3：TSS-DMR）中的印迹区域的分子破坏引起的印迹疾病。目前正在讨论三种已知的TS14亚型（缺失，母体单亲二体性（upd（14）mat），甲基化缺失（LOM））的频率，并且在LOM组中，多位点印记障碍（MLID）的发生被确定。我们目前有16例TS14患者的分子发生改变，影响了MEG3：TSS-DMR，包括7例LOM患者（43.8％），6例upd（14）mat携带者（37.5％）和3例患者缺失（18.8％）父MEG3：TSS-DMR。我们在LOM组中没有发现任何关于MLID的证据，包括两种情况下存在不同的组织。MEG3：TSS-DMR LOM患者及其父母（Trio WES）的全外显子组测序（WES）未发现明显的致病变异，可能导致印迹基因座的甲基化异常。通过将我们的数据与文献中的数据进行汇总，我们可以表明，影响临床相关印迹基因座的MLID在TS14中很少见，因此与与MLID相关的其他印迹疾病（例如Silver-Russell综合征（SRS）和Beckwith-Wiedemann综合征（ BWS）。但是，与TS14的临床重叠一致，在携带MLID的SRS患者中，MEG3：TSS-DMR经常受到影响。在TS14患者中，无法鉴定出导致MLID和胎儿MLID决定因素的母体效应变异体的已知候选基因变异体。因此，与BWS或SRS患者中的基因突变相比，14q32基因突变可能具有其他分子原因。