Growth retardation associated with a novel DNMT3A variation in a Chinese boy: A Case Report

Abstract

Abstract Background The human gene DNMT3A (DNA methyltransferase 3 alpha) is involved in DNA de novo methylation essential for genome regulation and development. Pathogenic variants in DNMT3A are most commonly associated with variable overgrowth (such as Tatton-Brown-Rahman Syndrome, TBRS), intellectual disability, autism spectrum disorder (ASD) and acute myeloid leukemia (AML). We identified a de novo DNMT3A variant in a Chinese boy with growth retardation. Case presentation A 2.8-year boy was hospitalized with a complaint of growth retardation for 24 months. He was born at 38 weeks of gestation. He showed obviously growth retardation since 3 months of age later, including weight and height. His motor and intellectual developmental milestone were slightly delayed. He began to rise head and turn over at 4 months, sit at 6 months, crawl at 7 months and work at 18 months, respectively. He began to speak a single word at 12 months and could speak few words at 2 years. At admission at 2.8 years of age, his weight was 9.6 kg (< P3th), height was 85.4 cm (< P3th), and head circumference was 45.2 cm (< P3th). He could run but could not jump with two feet, he could follow easy and simple instructions. Physical examination revealed no abnormal signs, especially no abnormal dysmorphic features. A de novo DNMT3A variant, c.911_913del (p.S304del), was identified using next-generation sequencing. His growth retardation was associated with DNMT3A variation. Conclusion We reported here the first case presented with growth retardation who was associated with a de novo DNMT3A variation in a Chinse boy. Our report has expanded on the clinical phenotype of the DNMT3A gene, which can also associated with growth retardation besides overgrowth.