【摘要】 目的　探讨共济失调毛细血管扩张症(ataxia telangiectasia,AT)的临床特征和ATM基因的突变特点。方法　应用聚合酶链反应、逆转录聚合酶链反应、聚丙烯酰胺凝胶电泳和DNA直接测序方法对2例临床诊断AT的患者及其父母ATM基因全编码区进行突变检测。结果　2例AT患者的临床特征为儿童期起病的进行性发展的小脑性共济失调,眼、皮肤毛细血管扩张以及免疫缺陷导致的反复感染;血清甲胎蛋白高于正常,免疫球蛋白IgA、IgG值低于正常;头颅MRI显示小脑萎缩,脑SPECT显示小脑局部脑血流(rCBF)灌注减少。共发现3种碱基变异。在1例患者中发现外显子11G1346C的错义突变,为一种纯合突变;在另1例患者中发现外显子6G610T的无义突变和外显子47C6679T的错义突变,为一种复合性杂合突变。突变位点均位于ATM基因功能域。结论　作出了2例AT患者的基因诊断。报道了3种新的ATM基因突变。更多还原

【Abstract】 Objective To investigate the clinical manifestation and mutation characteristics of ATM gene in Chinese patients with ataxia-telangiectasia(AT). Methods Sequence variants of the entire coding exons of ATM gene were tested using polymerase chain reaction(PCR), reverse transcription-polymerase chain reaction(RT-PCR), polyacrylamide gel electrophoresis(PAGE) and DNA direct sequencing in two Chinese patients clinically diagnozed as AT. Results The clinical characteristics of two AT patients were progressive cerebellar ataxia with ages at onset of childhood, ocular-cutaneous telangiectasia and recurrent pulmonary infection due to immuno- deficiency;the serum alpha fetoprotein(AFP) levels were higher than normal, the serum immunoglobin IgA and IgG levels were lower than normal;brain MRI showed cerebellar atrophy, brain SPECT showed cerebellar regional cerebral blood flow(rCBF) hypoperfusion to a certain degree. Totally three nucleotide changes were identified. A missense mutation of G1346C in exon 11, which was a homozygotic mutation, was identified in one patient; a nonsense mutation of G610T in exon 6 combined with a missense mutation of C6679T in exon 47, which was a compound heterozygotic mutation, were identified in the other patient. They were co-segregated with the disease and were localized within the functional domain of ATM gene. Conclusion We have made gene diagnoses for two Chinese AT patients, in which three novel ATM gene mutations were identified.更多还原