Integrated facial analysis and targeted sequencing identifies a novel KDM6A pathogenic variant resulting in Kabuki syndrome

• Main Authors: Weihui Shi, Yiyao Chen, Songchang Chen, Shuyuan Li, Chunxin Chang, Lanlan Zhang, Hongjun Fei, Hefeng Huang, Junyu Zhang, Chenming Xu
• Format: Article
• Language: English
• Published: Wolters Kluwer Health 2018-12-01
• Series: Journal of Bio-X Research
• Online Access: http://journals.lww.com/10.1097/JBR.0000000000000022
• ISSN: 2096-5672; 2577-3585

Abstract. Kabuki syndrome (KS) is a rare congenital mental retardation condition characterized by facial dysmorphia, visceral and skeletal malformations, and developmental delay. The integrated phenotype and genotype-based prioritization is critical for diagnoses of genetic diseases. In this study, a Chinese woman, presenting with characteristic facial features of KS, came for pre-pregnancy consultation. We aimed to clarify the diagnosis and provide pre-pregnancy genetic counseling. Facial dysmorphology analysis and next-generation sequencing-based multigene panel approach were used to identify candidate syndromes and causative variants, respectively. The candidate variant was verified by Sanger sequencing. We identified a novel de novo KDM6A pathogenic variant (c.3521G>A) in the woman, which was in line with the Face2Gene analysis result. Peripheral blood RNA assay showed that the variant transcript underwent the nonsense-mediated mRNA decay and led to subsequent haploinsufficiency of KDM6A. Our study provides the genetic diagnosis method for KS type 2 and identifies the first KDM6A point variant in Chinese patient.