Investigation Of A Family With Glanzmann’s Thrombasthenia Caused By Deletion/Insertion Mutation In GPⅢa Gene And Literature Review

Objective:To explore the molecular pathogenesis and genetic characteristics of 1 cases of Glanzmann’s thrombasthenia(GT)family,and to further explore the clinical manifestations,molecular biological characteristics of the Glanzmann’s thrombasthenia caused by ITGB3 gene and to identify the related diseases of hemorrhage-related diseases.Methods:The peripheral blood of a proband and her family members were collected.The proband was a 14-year-old female,who had skin and mucosal bleeding since childhood.After menstruation,she developed anemia symptoms due to increased menstrual volume and prolonged menstrual period.The patient’s mother and father had a consanguineous marriage.The proband was diagnosed with GT based on clinical manifestations,platelet aggregation and the expression of CD41 and CD61 in platelets.Whole-exome sequencing was used to detect genetic defects related to GT in the proband.Primers were designed according to the mutation site of the proband,and then the peripheral blood DNA of family members was amplified to verify the genetic characteristics of the pedigree. Retrieving literatures on gene mutations related to Glanzmann’s thrombasthenia from Wanfang,China How Net,Pub Med and other databases,analysis and summary mutations of pathogenic genes of ITGB3.Results:The proband had normal platelet counts and coagulation function.The platelets had a normal aggregation response to ristocetin but no obvious response to adenosine diphosphate,thrombin,collagen,arachidonic acid,or epinephrine.The expression of CD41 and CD61 was less than 5% in the platelets of the proband.Whole-exome sequencing showed a c.1784＿1802delins GTCACA homozygous mutation in exon 11 of the ITGB3 gene in the proband.The heterozygous mutation was found in the proband’s parents,grandmother,uncle,aunt and younger brother.Through database search,the ITGB3 gene mutation spectrum of 124 patients diagnosed with GT was summarized and analyzed.A total of 140 ITGB3 mutations were found to be associated with GT,including missense mutations,frameshift mutations,nonsense mutations,splice mutations,insertion or deletion mutations,etc.By molecular simulation of the mutated functional regions,the most prevalent disease mutation is the βI region of β3 integrin.Discussion:This GT pedigree was caused by a c.1784＿1802delins GTCACA mutation in exon 11 of the ITGB3 gene.We summarized the mutation characteristics of GT patients,it was found that the most common mutations occurred in βI region,followed by Hybrid region and EGF region.The correlation between the ITGB3 mutation site and the disease phenotype is not clear.