Recurrent 200-kb deletions of 16p11.2 that include the SH2B1 gene are associated with developmental delay and obesity
Recurrent 200-kb deletions of 16p11.2 that include the SH2B1 gene are associated with developmental delay and obesity
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DOI：
10.1097/gim.0b013e3181ef4286
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发表时间：
2010-10-01
影响因子：
8.8
通讯作者：
Tsuchiya, Karen D.
中科院分区：
文献类型：
--
作者：
Bachmann-Gagescu, Ruxandra;Mefford, Heather C.;Tsuchiya, Karen D.
目的：16号染色体的短臂富含片段性重复，使基因组的这一区域易于发生许多复发性重排。16p11.2（29.5-30.1 Mb）中约600 kb区域的基因组不平衡与自闭症、智力残疾、先天性异常和精神分裂症有关。然而，最近发现16p11.2（28.7-28.9 Mb）中一个单独的远端200 kb区域（包括SH 2B 1基因）与孤立性肥胖有关。本研究的目的是更好地确定这种复发性含SH 2B 1微缺失的表型，在一组表型异常的患者中，未选择肥胖。研究方法：在临床环境中对总共23，084名患者进行了阵列比较杂交，用于各种适应症，最常见的是发育迟缓。结果：在31例患者中发现了含SH 2B 1区域的缺失。与对照组相比（P = 0.003），缺失在患者人群中富集，包括遗传和新发事件。详细的临床资料可用于6名患者，他们都有不同严重程度的发育迟缓。6名患者中有4名患者的体重指数>= 95百分位数，支持先前描述的与肥胖的相关性。在17例患者中发现的相互重复，与对照组相比，在我们的患者人群中似乎没有显着富集。结论：16 p11.2 SH 2B 1区域的缺失是致病性的，除了肥胖外，还与发育迟缓有关。Genet Med 2010：12（10）：641-647.
Purpose: 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. Methods: 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. Results: 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. Conclusions: Deletions of the 16p11.2 SH2B1-containing region are pathogenic and are associated with developmental delay in addition to obesity. Genet Med 2010:12(10):641-647.