Kabuki syndrome: novel pathogenic variants, new phenotypes and review of literature

作者：Huakun Shangguan, Chang Su, Qian Ouyang, Bingyan Cao, Jian Wang, Chunxiu Gong, Ruimin Chen · 发表于：Orphanet Journal of Rare Diseases · 年份：2019 · DOI：10.1186/s13023-019-1219-x · 被引用次数：57 · 研究领域：Genomics and Rare Diseases、Genomic variations and chromosomal abnormalities、Genetic Syndromes and Imprinting

OBJECTIVE: This study describes 5 novel variants of 7 KMT2D/KDM6A gene and summarizes the clinical manifestations and the mutational spectrum of 47 Chinese Kabuki syndrome (KS) patients. METHODS: Blood samples were collected for whole-exome sequencing (WES) for 7 patients and their parents if available. Phenotypic and genotypic spectra of 40 previously published unrelated Chinese KS patients were summarized. RESULT: Genetic sequencing identified six KMT2D variants (c.3926delC, c.5845delC, c.6595delT, c.12630delG, c.16294C > T, and c.16442delG) and one KDM6A variant (c.2668-2671del). 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, 29.5% (5/17) patients had brain abnormalities, such as hydrocephalus, cerebellar vermis dysplasia, thin pituitary and white matter myelination delay, corpus callosum hypoplasia and Dandy-Walker malformation. CONCLUSION: In this report, five novel variants in KMT2D/KDM6A genes are described. A subset of Chinese KS patients presented with brain abnormalities that were not previously reported. Our study expands the mutational and phenotypic spectra of KS.