Identification of KMT2D and KDM6A variants by targeted sequencing from patients with Kabuki syndrome and other congenital disorders
| Autor: | Ivy Ng, Chui-Sun Yap, Teck Wah Ting, Saumya Shekhar Jamuar, Angeline H. M. Lai, Ee-Shien Tan, Ene-Choo Tan |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male DNA Mutational Analysis Mutation Missense DNA sequencing Congenital Abnormalities Cohort Studies 03 medical and health sciences 0302 clinical medicine INDEL Mutation Genetics medicine Missense mutation Humans Abnormalities Multiple Child Gene Asia Southeastern Histone Demethylases biology Infant Newborn High-Throughput Nucleotide Sequencing Infant General Medicine Sequence Analysis DNA medicine.disease Phenotype Hematologic Diseases Neoplasm Proteins DNA-Binding Proteins genomic DNA 030104 developmental biology Vestibular Diseases 030220 oncology & carcinogenesis Child Preschool Face biology.protein Demethylase Female Kabuki syndrome Congenital disorder |
| Zdroj: | Gene. 731 |
| ISSN: | 1879-0038 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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