全外显子组测序在一个三代家系中筛查格雷夫斯病易感基因。
Screening of Graves' disease susceptibility genes by whole exome sequencing in a three-generation family.
机构信息
Department of Endocrinology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510220, China.
Huizhou Health Sciences Polytechnic, Huizhou, China.
出版信息
BMC Med Genomics. 2021 Feb 10;14(1):46. doi: 10.1186/s12920-020-00865-z.
BACKGROUND
Graves' disease(GD) has a tendency for familial aggregation, but it is uncommon to occur in more than two generations. However, little is known about susceptibility genes for GD in the three-generation family.
METHODS
DNA were extracted from three-generation familial GD patient with a strong genetic background in a Chinese Han population. The Whole Exome Sequencing (WES) was utilized to screen the genome for SNVs associated with GD and the Sanger Sequencing was used to confirm the potential disease-causing genes.
RESULTS
In the case study, there were five patients with Graves' disease(GD) from a three-generation family. The SNVs of MAP7D2(c. 452C > T: p. A151V), SLC1A7(c. 1204C > T: p. R402C), TRAF3IP3(c. 209A > T: p. N70I), PTPRB(c. 3472A > G: p. S1158G), PIK3R3(c. 121C > T: p. P41S), DISC1(c. 1591G > C: p. G531R) were found to be associated with the familial GD and the Sanger sequencing had confirmed these variations. Furthermore, PolyPhen-2 score showed that the variants in TRAF3IP3, PTPRB, PIK3R3 are more likely to change protein functions.
CONCLUSION
The MAP7D2, SLC1A7, TRAF3IP3, PTPRB, PIK3R3, DISC1 may be the candidate susceptibility genes for familial GD from a three generations family.
背景
格雷夫斯病（GD）有家族聚集倾向，但在三代以上的家族中并不常见。然而，对于三代家族中 GD 的易感基因知之甚少。
方法
从一个具有强烈遗传背景的中国汉族三代家族 GD 患者中提取 DNA。利用全外显子组测序（WES）筛选与 GD 相关的 SNV，并利用 Sanger 测序证实潜在的致病基因。
结果
在本病例研究中，一个三代家族中有五名 Graves 病（GD）患者。MAP7D2（c.452C>T:p.A151V）、SLC1A7（c.1204C>T:p.R402C）、TRAF3IP3（c.209A>T:p.N70I）、PTPRB（c.3472A>G:p.S1158G）、PIK3R3（c.121C>T:p.P41S）、DISC1（c.1591G>C:p.G531R）的 SNVs 与家族性 GD 相关，Sanger 测序证实了这些变异。此外，PolyPhen-2 评分显示，TRAF3IP3、PTPRB、PIK3R3 中的变异更可能改变蛋白质功能。
结论
MAP7D2、SLC1A7、TRAF3IP3、PTPRB、PIK3R3、DISC1 可能是三代家族性 GD 的候选易感基因。
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