摘要：

目的 报道4 例经基因检测明确诊断的共济失调毛细血管扩张症患者，结合文献总结该病临床表型和基因突变特点。 方法 采集3 个共济失调毛细血管扩张症家系共4 例患者临床资料，并提取患者及其父母外周静脉血，采用全外显子测序和Sanger 测序进行ATM 基因突变分析。 结果 4 例共济失调毛细血管扩张症患者均表现为儿童期发病的进行性进展的小脑共济失调、球结膜和皮肤毛细血管扩张、免疫缺陷导致反复感染，血清甲胎蛋白水平升高，头部MRI 显示小脑萎缩。ATM 基因检测显示，例1 和例2 存在已知复合杂合突变c.8287C > T（p.Arg2763X）和c.9139C > T（p.Arg3047X），均为无义突变；例3 存在2 种未报道的复合杂合突变，包括无义突变c.8911C > T（p.Gln2971X）和缺失突变c.7141_7151delAATGGAAAAAT （p.Asn2381GlufsX18）; 例4 存在纯合突变 c.1402_1403delAA  （p.Lys468GlufsX18）。 结论 4 例患者具有典型共济失调毛细血管扩张症临床表现。变异型共济失调毛细血管扩张症患者神经系统受累较轻，头部MRI 通常正常，神经系统以外受累少见，明确诊断仍依靠ATM基因检测。

关键词: 共济失调性毛细血管扩张, 表型, 基因, 突变

Abstract:

Objective  To report 4 cases of ataxia-telangiectasia (AT) with ATM genetic mutation and to summarize the clinical and genetic characteristics of AT by literatures review.  Methods  Clinical data of 4 patients from 3 AT families was collected in detail and genomic DNA of the patients and family members was extracted from peripheral blood. Whole exon sequencing (WES) and polymerase chain reaction (PCR) of Sanger sequencing was used to analyse ATM genic mutation.  Results  Four patients were characterized by progressive cerebellar ataxia with onset in childhood, oculocutaneous telangiectasia, recurrent infection caused by immunodeficiency, α-fetoprotein (AFP) elevation and cerebellar atrophy shown in brain MRI were presented. Sequence analysis of ATM gene revealed two known compound heterozygous mutations c.8287C > T (p.Arg2763X) and c.9139C > T (p.Arg3047X) which were nonsense mutation in Case 1 and Case 2. In Case 3, there were two compound heterozygous mutations, including nonsence mutation c.8911C > T (p.Gln2971X) and deficit mutation c.7141_7151delAATGGAAAAAT (p.Asn2381GlufsX18) both of which were not reported previously. Case 4 carried homozygotic mutation c.1402_1403delAA (p. Lys468GlufsX18).  Conclusions  Four patients were diagnosed as AT with typical clinical manifestations. Patients with variant AT present mild nervous system symptom, normal head MRI and less involvement other than nervous systemt. Definite diagnosis should be dependant on ATM genetic testing.

Key words: Ataxia telangiectasia, Phenotype, Genes, Mutation