Ataxia-telangiectasia in China: a case report of a novel variant and literature review.

Background: 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.

Case Presentation: 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.

Conclusion: 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.