Zegers D, Hendrickx R, Verrijken A, Van Hoorenbeeck K, Van Camp J K, de Craemer V, Rooman R P, Desager K N, Massa G, Van Gaal L F, Van Hul W, Beckers S
Department of Medical Genetics, University of Antwerp, Antwerp University Hospital, Antwerp, Belgium.
Pediatr Obes. 2014 Feb;9(1):36-42. doi: 10.1111/j.2047-6310.2012.00131.x. Epub 2013 Jan 16.
What is already known about this subject BDNF is involved in the regulation of food intake and body weight. BDNF deficient animal models are obese. Chromosomal abnormalities cause obesity in humans. What this study adds Evaluation of point mutations in BDNF. Identification of BDNF mutations in obese children. Point mutations in BDNF are not a common cause of childhood obesity.
There is ample evidence that BDNF has a role in the regulation of food intake and body weight. Study of various mouse models gave a clear indication that BDNF deficiency leads to the development of obesity. Functional loss of one copy of the BDNF gene, due to chromosomal rearrangements or microdeletions, can cause an obesity phenotype in humans. Therefore, we wanted to investigate whether point mutations in the gene also result in a comparable phenotype.
We screened 554 severely overweight and obese children and adolescents and 565 lean adults for mutations in the coding region of BDNF. Mutation screening was performed by high-resolution melting curve analysis and direct sequencing.
Screening of obese patients led to the identification of two synonymous variations (V37V and H65H) and two non-synonymous coding mutations (T2I and V46M) in the BDNF gene. When we subsequently screened our control population, we found T2I with comparable frequency and confirmed that this is a rare and non-pathogenic variant. In addition, we found another non-synonymous mutation (N187S) in the control population.
In silico analysis of the V46M variant did not support a clear disease-causing effect and no family data were available in order to determine whether the mutation segregates with obesity. However, we cannot rule out a possible pathogenic effect for this variant. In general, we tend to conclude that mutations in the coding region of BDNF are uncommon in obese patients and are therefore not likely to play an essential role in the pathogenesis of childhood obesity.
关于该主题已知的信息：脑源性神经营养因子（BDNF）参与食物摄入和体重的调节。BDNF缺陷动物模型会出现肥胖。染色体异常会导致人类肥胖。本研究的补充内容：对BDNF中的点突变进行评估。在肥胖儿童中鉴定BDNF突变。BDNF中的点突变并非儿童肥胖的常见原因。
有充分证据表明BDNF在食物摄入和体重调节中起作用。对各种小鼠模型的研究清楚表明BDNF缺乏会导致肥胖的发生。由于染色体重排或微缺失导致BDNF基因一个拷贝的功能丧失，可在人类中引起肥胖表型。因此，我们想研究该基因中的点突变是否也会导致类似的表型。
我们对554名严重超重和肥胖的儿童及青少年以及565名瘦的成年人进行了BDNF编码区突变筛查。通过高分辨率熔解曲线分析和直接测序进行突变筛查。
对肥胖患者的筛查在BDNF基因中鉴定出两个同义变异（V37V和H65H）以及两个非同义编码突变（T2I和V46M）。随后我们对对照人群进行筛查时，发现T2I的频率相当，并证实这是一种罕见的非致病性变异。此外，我们在对照人群中发现了另一个非同义突变（N187S）。
对V46M变异的计算机分析不支持明确的致病作用，且没有家族数据来确定该突变是否与肥胖相关。然而，我们不能排除该变异可能存在的致病作用。总体而言，我们倾向于得出结论，BDNF编码区的突变在肥胖患者中并不常见，因此不太可能在儿童肥胖的发病机制中起关键作用。
