Alu-related 5q35 microdeletions in Sotos syndrome
Alu-related 5q35 microdeletions in Sotos syndrome
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DOI：
10.1111/j.1399-0004.2008.01032.x
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发表时间：
2008-10-01
影响因子：
3.5
通讯作者：
Matsumoto, N.
中科院分区：
文献类型：
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作者：
Mochizuki, J.;Saitsu, H.;Matsumoto, N.
由于5 q35微缺失或基因内突变导致的NSD 1基因单倍不足导致Sotos综合征（SoS）。在49例日本缺失病例中，46例共同缺失断点位于两个侧翼低拷贝重复序列（LCR），这意味着LCR之间的非等位基因同源重组（NAHR）是共同缺失的主要机制。在其他三个非典型缺失的情况下，缺失的机制仍然没有答案。我们采用荧光原位杂交（FISH）、实时定量聚合酶链反应（qPCR）和Southern印迹杂交来表征非典型微缺失。在核苷酸水平上成功地确定了三例病例中的所有缺失断点。两个缺失片段大小分别为1.07 Mb（SoS 19）和1.23 Mb（SoS 109），另一个缺失片段大小分别为28 kb和0.72 Mb，中间插入一个完整的29 kb片段（SoS 44）。所有缺失均小于典型的1.9-Mb常见缺失。在SoS 19的两个缺失断裂点、SoS 109的一个缺失断裂点和SoS 44的近端28-kb缺失的两个缺失断裂点中鉴定了Alu元件。至少在两种非典型缺失中强烈提示NAHR介导。最后，qPCR是一种非常有用的方法来确定甚至在重复相关区域中的缺失断点。
Haploinsufficiency of the NSD1 gene due to 5q35 microdeletions or intragenic mutations causes Sotos syndrome (SoS). In 46 of the 49 Japanese deletion cases, common deletion breakpoints were located at two flanking low copy repeats (LCRs), implying that non-allelic homologous recombination (NAHR) between LCRs is the major mechanism for the common deletion. In the other three cases of atypical deletions, the mechanism(s) of deletions remains unanswered. We characterized the atypical microdeletions using fluorescence in situ hybridization (FISH), quantitative real-time polymerase chain reaction (qPCR), and Southern blot hybridization. All the deletion breakpoints in the three cases were successfully determined at the nucleotide level. Two deletions are 1.07 Mb (SoS19) and 1.23 Mb (SoS109) in size, and another consisted of two deletions with sizes of 28 kb and 0.72 Mb, intervened by an intact 29-kb segment (SoS44). All deletions were smaller than a typical 1.9-Mb common deletion. Alu elements were identified in both deletion breakpoints in SoS19, one of deletion breakpoints in SoS109, and both deletion breakpoints of the proximal 28-kb deletion in SoS44. Alu-mediated NAHR is strongly suggested at least in two of atypical deletions. Finally, qPCR is a very useful method to determine deletion breakpoints even in repeat-related regions.