Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan.
J Hum Genet. 2012 Mar;57(3):191-6. doi: 10.1038/jhg.2011.154. Epub 2012 Jan 19.
Approximately 3% of the live-born infants have major dysmorphic features, and about two-thirds of which are observed in the maxillofacial region; however, in many cases, the etiology of the dysmorphic features remains uncertain. Recently, the genome-wide screening of large patient cohorts with congenital disorders has made it possible to discover genomic aberrations corresponding to the pathogenesis. In our analyses of more than 536 cases of clinically undiagnosed multiple congenital anomalies and mental retardation (MR) by microarray-based comparative genomic hybridization, we detected two non-consanguineous unrelated patients with microdeletions at 10p11.23-p12.1, which overlapped for 957 kb, including four protein-coding genes: ARMC4, MPP7, WAC and BAMBI. As the two patients had similar phenotypes; for example, MR and multiple maxillofacial abnormalities including midface retrusion, wide mouth and large tongue, we assessed the phenotypes in detail to define the common features, using quantitative evaluations of the maxillofacial dysmorphism. The concordance of the genetic and phenotypic alterations is a good evidence of a new syndrome. Although an interstitial deletion of 10p is rare, the current study is the first trial to examine precisely the craniofacial characteristics of patients with a heterozygous deletion at 10p11.23-p12.1, and presents good evidence to diagnose potential patients with the same genetic cause.
大约 3%的活产婴儿存在主要的畸形特征，其中约三分之二发生在颌面区域；然而，在许多情况下，畸形特征的病因仍然不确定。最近，对患有先天性疾病的大患者队列进行全基因组筛查，使得发现与发病机制相对应的基因组异常成为可能。在我们通过基于微阵列的比较基因组杂交对 536 例临床未诊断的多发性先天性畸形和智力障碍（MR）病例进行的分析中，我们检测到了两个非近亲相关的患者，他们在 10p11.23-p12.1 处存在微缺失，重叠了 957 kb，包括四个编码蛋白的基因：ARMC4、MPP7、WAC 和 BAMBI。由于这两个患者具有相似的表型；例如，MR 和多种颌面异常，包括中面部后缩、阔口和大舌，我们使用颌面畸形的定量评估详细评估了表型，以确定共同特征。遗传和表型改变的一致性是新综合征的一个很好证据。虽然 10p 的染色体间缺失很少见，但目前的研究首次精确检查了杂合性缺失 10p11.23-p12.1 的患者的颅面特征，并提供了很好的证据来诊断具有相同遗传原因的潜在患者。
