Ataxia telangiectasia is a rare autosomal recessive multisystem disorder caused by mutations in the gene of ATM serine/threonine kinase. It is characterized by neurodegeneration, leading to severe ataxia, immunodeficiency, increased cancer susceptibility, and telangiectasia. Here, we discovered a co-segregation of two ATM gene variants with ataxia telangiectasia in an Egyptian family. While one of these variants (NM_000051.4(ATM_i001):p.(Val128*)) has previously been reported as pathogenic, the other one (NM_000051.4(ATM_i001):p.(Val1729Leu)) is regarded as a variant of uncertain significance. Our findings in this family provide additional evidence for causality of the second variant and argue that its status should be changed to pathogenic.

共济失调毛细血管扩张症是一种罕见的常染色体隐性遗传多系统疾病，由 ATM 丝氨酸/苏氨酸激酶基因突变引起。它的特点是神经退行性变，导致严重的共济失调、免疫缺陷、癌症易感性增加和毛细血管扩张。在这里，我们在一个埃及家族中发现了两种ATM基因变异与共济失调毛细血管扩张症的共同分离。虽然这些变体之一 (NM_000051.4(ATM_i001):p.(Val128*)) 先前已被报告为致病性，但另一种 (NM_000051.4(ATM_i001):p.(Val1729Leu)) 被认为是意义不明。我们在这个家族中的发现为第二种变异的因果关系提供了额外的证据，并认为它的状态应该改变为致病性。