title: KMT2D p.Gln3575His segregating in a family with autosomal dominant choanal atresia strengthens the Kabuki/CHARGE connection.
abstract: Choanal atresia is rarely reported in Kabuki syndrome, but is a common feature of CHARGE syndrome. Otherwise, the two conditions have a number of overlapping features, and the molecular links between them have recently been elucidated. Here, we report a case of a mother and her two children who presented with congenital choanal atresia. We performed whole exome sequencing on DNA from the mother and her two unaffected parents, and identified a de novo, novel variant in KMT2D. KMT2D p.Gln3575His segregated with disease status in the family, and is associated with a unique and conserved phenotype in the affected family members, with features overlapping with Kabuki and CHARGE syndromes. Our findings further support the potential etiological link between these two classically distinct conditions. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Faculty of Medicine, Department of Genetics, Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Lauren
authors.initials: L
authors.lastname: Badalato
authors.affiliation: Department of Biochemistry and Medicine, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors.forename: Sali M K
authors.initials: SM
authors.lastname: Farhan
authors.affiliation: Department of Biochemistry and Medicine, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors.forename: Allison A
authors.initials: AA
authors.lastname: Dilliott
authors.affiliation: Faculty of Medicine, Departments of Pediatrics, Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Bulman
authors.affiliation: Department of Biochemistry and Medicine, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, London Health Sciences Centre, Western University, London, Ontario, Canada.|Medical Genetics, Department of Pediatrics, IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Sharan L
authors.initials: SL
authors.lastname: Goobie
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D019943:Amino Acid Substitution; D058747:CHARGE Syndrome / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002754:Choanal Atresia / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D002892:Chromosomes, Human, Pair 22; D003062:Codon; D004268:DNA-Binding Proteins / Q000235:genetics*; D003952:Diagnostic Imaging; D059472:Exome; D005145:Face / Q000002:abnormalities*; D019066:Facies; D005260:Female; D005799:Genes, Dominant; D056726:Genetic Association Studies; D006402:Hematologic Diseases / Q000175:diagnosis / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D010641:Phenotype; D015837:Vestibular Diseases / Q000175:diagnosis / Q000235:genetics*
chemical_list: D003062:Codon; D004268:DNA-Binding Proteins; C120898:KMT2D protein, human; D009363:Neoplasm Proteins
keywords: CHARGE syndrome; KMT2D; Kabuki syndrome; MLL2; whole exome sequencing