Sharp Andrew J, Selzer Rebecca R, Veltman Joris A, Gimelli Stefania, Gimelli Giorgio, Striano Pasquale, Coppola Antonietta, Regan Regina, Price Sue M, Knoers Nine V, Eis Peggy S, Brunner Han G, Hennekam Raoul C, Knight Samantha J L, de Vries Bert B A, Zuffardi Orsetta, Eichler Evan E
Department of Genome Sciences, University of Washington School of Medicine, 1705 NE Pacific Street Seattle, WA 98195, USA.
Hum Mol Genet. 2007 Mar 1;16(5):567-72. doi: 10.1093/hmg/ddm016. Epub 2007 Mar 14.
We describe multiple individuals with mental retardation and overlapping de novo submicroscopic deletions of 15q24 (1.7-3.9 Mb in size). High-resolution analysis showed that in three patients both proximal and distal breakpoints co-localized to highly identical segmental duplications (>51 kb in length, > 94% identity), suggesting non-allelic homologous recombination as the likely mechanism of origin. Sequencing studies in a fourth individual provided base pair resolution and showed that both breakpoints in this case were located in unique sequence. Despite the differences in the size and location of the deletions, all four individuals share several major features (growth retardation, microcephaly, digital abnormalities, hypospadias and loose connective tissue) and resemble one another facially (high anterior hair line, broad medial eyebrows, hypertelorism, downslanted palpebral fissures, broad nasal base, long smooth philtrum and full lower lip), indicating that this represents a novel syndrome caused by haploinsufficiency of one or more dosage-sensitive genes in the minimal deletion region. Our results define microdeletion of 15q24 as a novel recurrent genomic disorder.
我们描述了多名患有智力障碍且15q24存在从头发生的重叠亚显微缺失（大小为1.7 - 3.9 Mb）的个体。高分辨率分析显示，在三名患者中，近端和远端断点均共定位于高度相同的节段性重复序列（长度>51 kb，同一性>94%），提示非等位基因同源重组可能是其起源机制。对第四名个体的测序研究提供了碱基对分辨率，并表明该病例中的两个断点均位于独特序列中。尽管缺失的大小和位置存在差异，但所有四名个体都具有几个主要特征（生长发育迟缓、小头畸形、手指异常、尿道下裂和疏松结缔组织），并且面部彼此相似（前发际线高、内侧眉毛宽、眼距增宽、睑裂下斜、鼻基底宽、人中长且平滑、下唇丰满），这表明这代表了一种由最小缺失区域中一个或多个剂量敏感基因单倍剂量不足引起的新型综合征。我们的结果将15q24微缺失定义为一种新型复发性基因组疾病。
