To explore the clinical characteristics and genetic basis for a child with global developmental delay and autism.
A child who had presented at West China Second University Hospital of Sichuan University on April 13, 2021 was selected as the study subject. Clinical manifestations, laboratory examination and result of genetic testing were analyzed.
The main symptoms of the child had included cognitive, language and motor delay, autism and epilepsy. Electroencephalogram revealed multiple focal discharges in both waking and sleeping stages, with the remarkable one seen at the sleeping stage. Cranial MRI showed pachygyria and local cortical thickening, Whole exome sequencing (WES) revealed that the child has harbored a heterozygous c.1589_1595dup (p.Gly533Leufs*143) frameshifting variant in the TBR1 gene (OMIM 604616). Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic (PS2+PVS1_Supporting+PM2_Supporting). After treated with levetiracetam and rehabilitation training, the child did not have seizure in the past 5 months, and his motor development has also significantly improved.
The c.1589_1595dup variant of the TBR1 gene probably underlay the disease in this patient.