Riehmer Vera, Erger Florian, Herkenrath Peter, Seland Saskia, Jackels Miriam, Wiater Alfred, Heller Raoul, Beck Bodo B, Netzer Christian
Institute of Human Genetics, University Hospital of Cologne, Cologne, Germany.
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
Am J Med Genet A. 2017 Aug;173(8):2132-2138. doi: 10.1002/ajmg.a.38285. Epub 2017 Jun 2.
Recently, a new syndrome with intellectual disability (ID) and dysmorphic features due to deletions or point mutations within the TBL1XR1 gene located in the chromosomal band 3q26.32 has been described (MRD41, OMIM 616944). One recurrent point mutation in the TBL1XR1 gene has been identified as the cause of Pierpont syndrome (OMIM 602342), a distinct intellectual disability syndrome with plantar lipomatosis. In addition, different de novo point mutations in the TBL1XR1 gene have been found in patients with autism spectrum disorders (ASD) and intellectual disability. Here, we report four patients from two unrelated families in whom array-CGH analysis and real-time quantitative PCR of genomic DNA revealed a TBL1XR1-microduplication. Adjacent genes were not affected. The microduplication occurred as a de novo event in one patient, whereas the other three cases occurred in two generations of a second, unrelated family. We compare and contrast the clinical findings in TBL1XR1 microdeletion, point mutation, and microduplication cases and expand the TBL1XR1-associated phenotypic spectrum. ID, hearing loss, and ASD are common features of TBL1XR1-associated diseases. Our clinical observations add to the increasing evidence of the role of TBL1XR1 in brain development, and they simultaneously demonstrate that different genetic disease mechanisms affecting TBL1XR1 can lead to similar ID phenotypes. The TBL1XR1-microduplication syndrome is an intellectual disability/learning disability syndrome with associated incomplete penetrance ASD, hearing loss, and delay of puberty. Its phenotypic overlap indicates that it is a genomic sister-disorder to the 3q26.32 microdeletion syndrome.
最近，已经描述了一种新的综合征，其具有智力残疾（ID）和畸形特征，是由位于染色体带3q26.32的TBL1XR1基因内的缺失或点突变引起的（MRD41，OMIM 616944）。TBL1XR1基因中的一个复发性点突变已被确定为皮尔庞特综合征（OMIM 602342）的病因，这是一种伴有足底脂肪瘤的独特智力残疾综合征。此外，在自闭症谱系障碍（ASD）和智力残疾患者中发现了TBL1XR1基因的不同新生点突变。在这里，我们报告了来自两个不相关家庭的四名患者，其中基因组DNA的阵列比较基因组杂交（array-CGH）分析和实时定量PCR显示存在TBL1XR1微重复。相邻基因未受影响。该微重复在一名患者中作为新生事件发生，而其他三例发生在第二个不相关家庭的两代人中。我们比较并对比了TBL1XR1微缺失、点突变和微重复病例的临床发现，并扩展了TBL1XR1相关的表型谱。ID、听力损失和ASD是TBL1XR1相关疾病的常见特征。我们的临床观察增加了越来越多的证据，证明TBL1XR1在大脑发育中的作用，同时表明影响TBL1XR1的不同遗传疾病机制可导致相似的ID表型。TBL1XR1微重复综合征是一种智力残疾/学习障碍综合征，伴有不完全外显的ASD、听力损失和青春期延迟。其表型重叠表明它是3q26.32微缺失综合征的基因组姐妹疾病。
