Division of Genetic Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington, USA.
Genet Med. 2010 Oct;12(10):641-7. doi: 10.1097/GIM.0b013e3181ef4286.
The short arm of chromosome 16 is rich in segmental duplications, predisposing this region of the genome to a number of recurrent rearrangements. Genomic imbalances of an approximately 600-kb region in 16p11.2 (29.5-30.1 Mb) have been associated with autism, intellectual disability, congenital anomalies, and schizophrenia. However, a separate, distal 200-kb region in 16p11.2 (28.7-28.9 Mb) that includes the SH2B1 gene has been recently associated with isolated obesity. The purpose of this study was to better define the phenotype of this recurrent SH2B1-containing microdeletion in a cohort of phenotypically abnormal patients not selected for obesity.
Array comparative hybridization was performed on a total of 23,084 patients in a clinical setting for a variety of indications, most commonly developmental delay.
Deletions of the SH2B1-containing region were identified in 31 patients. The deletion is enriched in the patient population when compared with controls (P = 0.003), with both inherited and de novo events. Detailed clinical information was available for six patients, who all had developmental delays of varying severity. Body mass index was ≥95th percentile in four of six patients, supporting the previously described association with obesity. The reciprocal duplication, found in 17 patients, does not seem to be significantly enriched in our patient population compared with controls.
Deletions of the 16p11.2 SH2B1-containing region are pathogenic and are associated with developmental delay in addition to obesity.
16 号染色体短臂富含片段重复序列，使该基因组区域容易发生多种反复出现的重排。16p11.2（29.5-30.1Mb）约 600kb 区域的基因组不平衡与自闭症、智力障碍、先天性异常和精神分裂症有关。然而，最近发现 16p11.2 上一个单独的、远端 200kb 区域（28.7-28.9Mb），包含 SH2B1 基因，与单纯性肥胖有关。本研究的目的是在一组非肥胖表型异常患者中，更好地定义这种反复出现的含有 SH2B1 的微缺失的表型。
在临床环境中对总共 23084 名患者进行了微阵列比较杂交，这些患者的适应证多种多样，最常见的是发育迟缓。
在 31 名患者中发现了含有 SH2B1 的区域缺失。与对照组相比，该缺失在患者群体中更为丰富（P = 0.003），包括遗传和新生事件。对六名患者进行了详细的临床信息，他们都有不同严重程度的发育迟缓。六名患者中有四名的体重指数≥第 95 百分位数，支持先前描述的与肥胖的关联。在 17 名患者中发现的互补重复似乎没有在我们的患者群体中与对照组相比明显富集。
16p11.2 含有 SH2B1 的区域缺失是致病性的，除了肥胖外，还与发育迟缓有关。
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