Objective: Report 5 new variants of 7 KMT2D/KDM6A and summarize the clinical manifestations and the mutational spectrum of Kabuki syndrome (KS) by analyzing the reported Chinese cases.
Methods: Blood samples were collected for whole-exome sequencing (WES) for 7 patients and their parents if available. Phenotypic and genotypic spectra of 39 previously published unrelated Chinese KS patients were summarized.
Result: Genetic sequencing identified six variants (c.3926delC, c.5845delC, c.6595delT, c.12630delG, c.16294C>T, and c.16442delG) in KMT2D gene and one variant (c.2668-2671del) in KDM6A gene. Of them, 4 variants (c.3926delC, c.5845delC, c.12630delG, and c.16442delG) in KMT2D gene and the variant (c.2668-2671del) in KDM6A gene were novel. Combining with previously published Chinese KS cases, the patients presented with five cardinal manifestations including facial dysmorphism, intellectual disability, growth retardation, fingertip pads and skeletal abnormalities. In addition, 25% (4/16) patients showed brain abnormalities, such as cerebellar vermis dysplasia, thin pituitary and white matter myelination delay, corpus callosum hypoplasia and Dandy-Walker malformation.
Conclusion: We reported five novel variants in KMT2D/KDM6A genes. A subset of Chinese KS patients presented with brain abnormalities that were not previously reported. Our study expended the mutational and phenotypic spectra of KS.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology