A novel ATAD3 duplication in a Chinese patient with epilepsy and hyperlactacidemia expands the range of clinical phenotype of 1p36.33 duplication syndrome

Background: Heterozygous duplication within the ATAD3 gene cluster can cause autosomal dominant chromosome 1p36.33 duplication syndrome, a rare and fatal multisystemic disorder, characterized by lethal perinatal cardiomyopathy, persistent hyperlactacidemia, and corneal clouding or cataracts, resulting in death in the first weeks of life. Methods Herein, we report a case of a 4-month, 27-day-old Chinese boy with only epilepsy and hyperlactacidemia who died at 6 months and 17 days of epilepsia partialis continua. The patient’s DNA was sequenced using whole-exome sequencing and whole-genome sequencing. Results We identified a de novo heterozygous duplication in the ATAD3 locus with breakpoints in exon 8 of ATAD3A and intron 3 of ATAD3C , creating a fusion gene, ATAD3A‒C , which codes for dozens of amino acid changes compared to that by ATAD3A . Conclusion We identified a de novo duplication in the ATAD3 locus in a Chinese boy. Contrary to previous case studies, the main clinical features were epilepsy and hyperlacticaemia. He survived for more than 6 months without lethal perinatal cardiomyopathy and corneal clouding or cataracts.