The patient was an 8-year-old boy, who presented with gradually progressive unilateral ptosis at the age of 6 years, which developed to bilateral ptosis at 8 years and 4 mo. The patient was an 8-year-old boy with bilateral ptosis. At the end of December 2017, the patient developed a fever of unknown origin, with his body temperature found to be as high as 38.5 °C. He recovered after being given oral antipyretics. One week after the fever, the patient had a stroke of dyskinesia and kept tilting his head to the left (cervical dyskinesia), a phenomenon that was accompanied by eye movement disorders. The patient was the first child born to non-consanguineous parents, and there are no similarly affected family members. Although he had a “history of congenital heart disease,” subsequent cardiac color Doppler ultrasound examination revealed normal results. The patient had no developmental milestone delays. Physical examination revealed that he had bilateral upper eyelid dropping (50% pupils covered). Moreover, he had limited abduction in the right eye, neck dystonia, and slightly reduced (degree 5-) muscle strength in bilateral lower limbs, while his bilateral knee reflexes disappeared. He also exhibited right cryptorchidism and a small penis. He could neither squat nor jump on one foot. Blood tests showed unremarkable results. Notably, he had a blood acetylcholine receptor antibody level of 0.82 nmol/L, while IgG tests for anti-MuSK, anti-Titin antibody, and human low-density lipoprotein receptor-related protein 4 were negative. Brain magnetic resonance imaging revealed diffused signals in the occipital, parietal cortex, and basal ganglia. His right ptosis was better, although it did not disappear after treatment with prednisone, neostigmine, and omeprazole from January 2018 to October 2019. His eye lid dropping reappeared in March 2020 and progressed to be bilateral. In August 2019, he was hospitalized due to a recurrent headache and was unresponsive to mannitol and carbamazepine. The patient was currently in the first grade of elementary school with medium grades. Whole exome libraries were prepared using the xGen Exome Research Panel v1.0 (IDT, Iowa, United States) and sequenced on the Novaseq 6000 platform (Illumina, San Diego, CA, United States). Raw data were cleaned using the fastp software package. Subsequently, the paired-end reads were performed using Burrows-Wheeler Aligner to the Ensemble GRCh37/hg19 reference genome. Synonymous and short indel calling were conducted using GATK software package followed by ANNOVAR annotation. Prediction was performed using the Provean, Sift, Polypen2_hdiv, Polypen2_hvar, Mutationtaster, M-Cap, and Revel software packages. The pathogenicity of all the variants was interpretated according to the guidelines of the American College of Medical Genetics and Genomics. We performed CNV-sequencing[], a CNV detection method based on high-throughput sequencing, in the patient. Briefly, genomic DNA was first sheared to 200-300 bp fragments via sonication, then subjected to quality control via electrophoresis. Ends of DNA fragments were patched using a DNA repair enzyme system to generate blunt ends, then a single adenine nucleotide was added to the 3’ end to form an overhanging A-tail. Subsequently, the genome was amplified by ligation-mediated PCR for 4-6 cycles. We used the same sequencing platform and data cleaning protocols to detect CNVs with a length of 100 kB and above using Chigene independently developed software packages. After that, we employed Decipher, ClinVar, OMIM, DGV, and ClinGen for annotation. At least 2 mL peripheral blood was collected from the patient, and mitochondrial DNA was extracted using the mitochondrial DNA extraction kit. Full-length mitochondrial DNA was amplified and purified via PCR, using the high-fidelity DNA polymerase and visualized via agarose gel electrophoresis. Paired-ended 150 bp sequencing was performed on the Novaseq6000 sequencing system. The sequenced data was aligned to reference sequence of NC_012920 (human complete mitochondrial genome 16569 bp circular DNA) using the Burrows-Wheeler Aligner software. The variants were then mapped onto the MITOMAP database, while pathogenicity was performed according to the MITOtip. Whole-exome sequencing sequencing results revealed no suspected disease-causing variants. Next, we employed the CNV analysis method (developed by Chigene) on whole-exome sequencing data and found that two deletions of the neighboring region of Chr16:15,125,591-16326688 (approximately 1.20 Mb) and 9857005-14989502 (approximately 5.13 Mb). CNV sequencing data revealed de novo heterozygous deletion of chr16:9699585-16928372 (approximately 7.23 Mb). Next, we compared this region and central nervous system phenotype with Decipher patients previously documented. Genes related to OMIM disorders are listed in Table. The mitochondrial DNA sequencing revealed negative results.