title: Identification of compound heterozygous mutations in the ITGA2B gene in a Chinese patient with Glanzmann thrombasthenia.
abstract: BACKGROUND
  Glanzmann thrombasthenia (GT) is an autosomal recessive bleeding disorder characterized by the tendency to hemorrhage and the inability of platelets to aggregate in response to agonists. GT is caused by a defect of the platelet glycoprotein IIb/IIIa complex. The objective of this study was to describe the clinical features and the genetic cause of GT in a 6-year-old girl from south China.
  
  
  METHODS
  A three-generation family was studied. The proband patient aged 6 years and her parents undertook examinations of platelet counts, blood film, bleeding time, platelet aggregation, and flow cytometry. All coding exons of the ITGA2B and ITGB3 genes were amplified by polymerase chain reaction (PCR), and direct sequencing was performed for mutational screening on the patient and normal controls consisted of 52 healthy blood donors. Reverse transcription PCR was conducted to test for exon skipping.
  
  
  RESULTS
  The proposita patient showed dispersing platelets, prolonged bleeding time, and severely reduced platelet aggregation in response to the physiological agonists adenosine diphosphate (ADP), epinephrine, collagen, and ristocetin. Flow cytometric measurements showed that the contents of alphaIIb and beta3 were significantly decreased. Sequencing results demonstrated two different types of heterozygous mutations existed in the alphaIIb gene (c.2930delG and IVS15-1delG). The compound mutations were also confirmed in the patient's mother and father separately.
  
  
  CONCLUSIONS
  The alphaIIbbeta3 deficiency of the proband was caused by two compound ITGA2B mutations, which were first reported in Chinese GT patients. The IVS15-1delG was first confirmed to cause an exon skipping.
authors.affiliation: Department of Laboratory Medicine, Third People's Hospital of Wenzhou, Wenzhou, Zhejiang 325000, China.
authors.forename: Jia-yong
authors.initials: JY
authors.lastname: Zheng
authors.forename: Yan-hui
authors.initials: YH
authors.lastname: Jin
authors.forename: Yong-lin
authors.initials: YL
authors.lastname: Zhu
authors.forename: Pei-pei
authors.initials: PP
authors.lastname: Jin
authors.forename: De-ting
authors.initials: DT
authors.lastname: Zhang
authors.forename: Zi-bing
authors.initials: ZB
authors.lastname: Jin
mesh_terms: D044466:Asian People; D002648:Child; D005260:Female; D005434:Flow Cytometry; D006579:Heterozygote; D006801:Humans; D039421:Integrin alpha2 / Q000235:genetics*; D039661:Integrin beta3 / Q000235:genetics; D009154:Mutation; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013915:Thrombasthenia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: C056564:ITGA2B protein, human; C061248:ITGB3 protein, human; D039421:Integrin alpha2; D039661:Integrin beta3