Shao Li, Wang Haoyi, Xu Jianbo, Qi Ming, Yu Zhaonan, Zhang Jing
Department of Child Healthcare, Jinhua Maternity and Child Health Care Hospital, Jinhua, Zhejiang, China.
Hangzhou D.A. Medical Laboratory, Hangzhou, Zhejiang, China.
Front Neurol. 2023 Jul 26;14:1228810. doi: 10.3389/fneur.2023.1228810. eCollection 2023.
Ataxia-telangiectasia (A-T) is a multisystem genetic disorder involving ataxia, oculocutaneous telangiectasia, and immunodeficiency caused by biallelic pathogenic variants in the gene. To date, most variants have been reported in the Caucasian population, and few studies have focused on the genotype-phenotype correlation of A-T in the Chinese population. We herein present a Chinese patient with A-T who carries compound heterozygous variants in the gene and conducted a literature review for A-T in China.
A 7-year-old Chinese girl presented with growth retardation, ataxia, medium ocular telangiectasia, cerebellar atrophy, and elevated serum alpha-fetoprotein (AFP) level, which supported the suspicion of A-T. Notably, the serum levels of immunoglobulins were all normal, ruling out immunodeficiency. Exome sequencing and Sanger sequencing revealed two likely pathogenic variants, namely NM_000051.4: c.4195dup (p.Thr1399Asnfs15) and c.6006 + 1G>T (p.?), which were inherited from her father and mother, respectively. From the Chinese literature review, we found that there was a marked delay in the diagnosis of A-T, and 38.9% (7/18) of A-T patients did not suffer from immunodeficiency in China. No genotype-phenotype correlation was observed in this group of A-T patients.
These results extend the genotype spectrum of A-T in the Chinese population and imply that the diagnosis of A-T in China should be improved.
共济失调毛细血管扩张症（A-T）是一种多系统遗传性疾病，由该基因的双等位基因致病变异引起，涉及共济失调、眼皮肤毛细血管扩张和免疫缺陷。迄今为止，大多数变异已在白种人群中报道，很少有研究关注中国人群中A-T的基因型-表型相关性。我们在此报告一名携带该基因复合杂合变异的中国A-T患者，并对中国的A-T进行文献综述。
一名7岁中国女孩表现出生长发育迟缓、共济失调、中度眼毛细血管扩张、小脑萎缩和血清甲胎蛋白（AFP）水平升高，这支持了A-T的怀疑。值得注意的是，免疫球蛋白血清水平均正常，排除了免疫缺陷。外显子组测序和桑格测序揭示了两个可能的致病变异，即NM_000051.4:c.4195dup（p.Thr1399Asnfs15）和c.6006+1G>T（p.?），分别从她的父亲和母亲遗传而来。从中国文献综述中，我们发现A-T的诊断存在明显延迟，在中国38.9%（7/18）的A-T患者没有免疫缺陷。在这组A-T患者中未观察到基因型-表型相关性。
这些结果扩展了中国人群中A-T的基因型谱，并表明中国应改善A-T的诊断。
