ESPE Abstracts (2019) 92 P2-177

Five Novel Variants of KMT2D/KDM6A Found in Seven Chinese Patients with Kabuki syndrome and a Literature Review of 39 Patients Reported in China

Ruimin Chen1, Chunxiu Gong2, Huakun Shangguan1, Chang Su2, Qian Ouyang1, Bingyan Cao2, Jian Wang3

1Fuzhou Children's Hospital of Fujian Province, Fujian Medical University Teaching Hospital, Fuzhou, China. 2The Capital Medical University Affiliated Beijing Children Hospital, Beijing, China. 3Shanghai Children's Medical Central Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China

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.

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