Garcia Loida Corbillon, Breillat Christelle, Lima Margarida, Combrié Robert, Morais Sara, Teixera Maria dos Anjos, Campos Manuel, Justica Benvindo, Nurden Alan T
Hospital de Santo Antonio, Serviço de Hematologia Clinica, Porto, Portugal.
Platelets. 2004 Feb;15(1):15-22. doi: 10.1080/0953710032000158754.
Glazzmann thrombasthenia is an inherited bleeding syndrome in which an absence of platelet aggregation is associated with quantitative or qualitative deficiencies of the alphaIIbbeta3 integrin. We now describe biochemical and molecular studies on two Portuguese families where platelets lack both surface and intracellular pools of alphaIIbbeta3. DNA extraction was followed by PCR-SSCP analysis of all exons and intronic boundaries in the alphaIIb and beta3 genes. Migration abnormalities were found for PCR fragments encompassing exon 12 (family 1) and exon 10 (family 2). For patient 1, there was a homozygous G to T transition at position 1846 which resulted in a stop codon at codon 616 in the beta3 gene. For patient 2, direct sequencing revealed a homozygous 1347C insert which led to a stop codon at codon 444 in the beta3 gene. For both patients a single mutated allele was inherited from each parent. Evidence is accumulating that nonsense mutations leading to a truncated beta3 may be a frequent cause of type I Glanzmann thrombasthenia in the Iberian peninsula.
血小板无力症是一种遗传性出血综合征，其中血小板聚集缺乏与αIIbβ3整合素的数量或质量缺陷相关。我们现在描述对两个葡萄牙家族的生化和分子研究，这两个家族的血小板缺乏αIIbβ3的表面池和细胞内池。提取DNA后，对αIIb和β3基因的所有外显子和内含子边界进行PCR-SSCP分析。在包含外显子12（家族1）和外显子10（家族2）的PCR片段中发现迁移异常。对于患者1，在位置1846处有一个纯合的G到T转换，导致β3基因中第616密码子处出现终止密码子。对于患者2，直接测序显示有一个纯合的1347C插入，导致β3基因中第444密码子处出现终止密码子。对于这两名患者，每个亲本都遗传了一个单一的突变等位基因。越来越多的证据表明，导致β3截短的无义突变可能是伊比利亚半岛I型血小板无力症的常见原因。
