RNA sequencing combining with whole exome sequencing reveals a compound heterozygous variant in ATM in a girl with atypical ataxia-telangiectasia.

Ataxia-telangiectasia (A-T) is an infrequent autosomal recessive multisystem disorder characterized by progressive cerebellar ataxia, oculo-cutaneous telangiectasia, a tendency to malignancies and variable immunodeficiency. Here we described a 5-year-old girl with atypical A-T symptoms. And 2 different ATM variants c.5939_5948del in exon 40 and c.2639-384A > G in intron 17 were detected by whole exome sequencing (WES) combined with RNA sequencing (RNA-seq). The variant spectrum of ATM was expanded. RNA-seq makes up for deficiencies of WES. We proposed a new approach, a dual-omics that combines RNA-seq with WES, for the diagnosis of genetic diseases. Moreover, our study discussed the phenotypic heterogeneity of A-T among family members as well as individuals. For children with recurrent infections and immunodeficiency, we suggested focusing on A-T after the exclusion of other potential diseases.