In this case study, it presents a rare familial GD case in 5 patients in a three-generation family. The five patients are consistent with the general characteristic of GD patients which is that the GD is prone to attack women at the age of 30-60 . All the members of the three-generation family came from the same district of Zhanjiang city and they have been living in similar environment which guarantees the consistency of environmental factors in this case study. Although the etiology of GD is complex and clear identification of potential factors for GD has not been completed, it is widely recognized that the genetic determinants contribute to the risk of GD such as HLA, CTLA-4, PTPN22, and CD40. However, no variation of these former identified genes were found, but the following variations of MAP7D2, SLC1A7, TRAF3IP3, PTPRB, PIK3R3, DISC1, and SUPT20HL were found in this familial GD. Furthermore, the variations in PTPRB, PIK3R3, and TRAF3IP3 were predicted that they may alter the functions of the encoded protein. Familial GD of multigeneration is important for heritable studies because it avoids the genetic heterogeneity factor, therefore, this case study may explain the genetic cause of the familial clustering of GD.
MAP7D2 (MAP7 domain containing 2) was located on X chromosome. MAP7D2 is specifically expressed in human brain tissue which has impact on the behavioral traits and cognition in human. MAP7D2 is also associated with sex-biased mental illnesses. Previous studies also show that gender predisposition to GD is associated with X chromosome inactivation (XCI) migration. Thus, the study on MAP7D2 is likely to provide important general information about the reason why women are more vulnerable to GD. SLC1A7 and DISC1 are also susceptibility genes for mental illnesses. In one research, Keith A. Young et al. discovered that DISC1 gene plays a vital role in post-traumatic stress disorder (PTSD) severity of US military veterans. In another research, Fujita K, et al. revealed that SLC1A7 gene expression in peripheral blood leukocytes is responsible for the association between socioeconomic status and depressive mood in healthy adults. We speculated that SLC1A7 and DISC1 may work in regulating the symptoms of GD such as nervousness, irritability and irritability.
The protein encoded by PTPRB belongs to the family of protein tyrosine phosphatases(PTP). The activation of PTK(protein tyrosine kinase) was regulated through the binding the SH2 domains of PI3K(PIK3R3 gene encode). The balance of tyrosine protein phosphorylation was regulated by PTP/PTK which participated in cell signal transduction, and regulates cell growth, differentiation, metabolism, transcription, immune responses, etc. Researches have demonstrated that the significant role of PTKs and PTPs is to modulate the tyrosine phosphorylation-dependent signaling pathways which is critical for the effector of NK cell and Neutrophil cell[13,14]. TRAF3IP3 is highly expressed in CD34+CD38+CD7+ common lymphoid progenitors (CLPs) and on the other hand, CD34+CD38+CD7+ cells have the capacity to differentiate into B/NK/T cell, which implies TRAF3IP3 possibly plays a role in lymphoid development. The over-activation of the T/B cell was regulated by CTLA-4 and CD40 gene variants which has been confirmed in the pathogenesis of autoimmune diseases including GD. Therefore, further study is necessary to figure out whether the variations of PTPRB, PIK3R3 and TRAF3IP3 are involved in the dysfunction of thyroid autoimmune.