1. Identification of KMT2D and KDM6A variants by targeted sequencing from patients with Kabuki syndrome and other congenital disorders.
- Author
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Yap CS, Jamuar SS, Lai AHM, Tan ES, Ng I, Ting TW, and Tan EC
- Subjects
- Abnormalities, Multiple epidemiology, Asia, Southeastern epidemiology, Child, Child, Preschool, Cohort Studies, Congenital Abnormalities epidemiology, DNA Mutational Analysis methods, Female, Hematologic Diseases epidemiology, High-Throughput Nucleotide Sequencing, Humans, INDEL Mutation, Infant, Infant, Newborn, Male, Mutation, Missense, Phenotype, Sequence Analysis, DNA, Vestibular Diseases epidemiology, Abnormalities, Multiple genetics, Congenital Abnormalities genetics, DNA-Binding Proteins genetics, Face abnormalities, Hematologic Diseases genetics, Histone Demethylases genetics, Neoplasm Proteins genetics, Vestibular Diseases genetics
- Abstract
Kabuki syndrome (KS) is a rare congenital disorder characterized by distinctive facies, postnatal growth deficiency, cardiac defects and skeletal anomalies. Studies have determined that pathogenic variants of the lysine-specific methyltransferase 2D (KMT2D) and lysine-specific demethylase 6A (KDM6A) genes are the major causes of KS. The two genes encode different histone-modifying enzymes that are found in the same protein complex that is critical for cell differentiation during development. Here we report the results from next-generation sequencing of genomic DNA from 13 patients who had a clinical diagnosis of KS based on facial dysmorphism and other KS-specific cardinal phenotypes. Nine of the 13 patients were confirmed to be carrying heterozygous pathogenic KMT2D variants, seven of which were truncating and two were missense substitutions. Overall, we uncovered 11 novel variants - nine in KMT2D and two in KDM6A. Seven of the novel variants (all KMT2D) were likely causative of the KS phenotype. Our study expands the number of naturally occurring KMT2D and KDM6A variants. The discovery of novel pathogenic variants will add to the knowledge on disease-causing variants and the relevance of missense variants in KS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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