title: De Novo variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner syndrome in two unrelated individuals identified by clinical exome sequencing.
abstract: BACKGROUND
  Wiedemann-Steiner Syndrome (WSS) is characterized by short stature, a variety of dysmorphic facial and skeletal features, characteristic hypertrichosis cubiti (excessive hair on the elbows), mild-to-moderate developmental delay and intellectual disability. [MIM#: 605130]. Here we report two unrelated children for whom clinical exome sequencing of parent-proband trios was performed at UCLA, resulting in a molecular diagnosis of WSS and atypical clinical presentation.
  
  
  METHODS
  For patient 1, clinical features at 9 years of age included developmental delay, craniofacial abnormalities, and multiple minor anomalies. Patient 2 presented at 1 year of age with developmental delay, microphthalmia, partial 3-4 left hand syndactyly, and craniofacial abnormalities. A de novo missense c.4342T>C variant and a de novo splice site c.4086+G>A variant were identified in the KMT2A gene in patients 1 and 2, respectively.
  
  
  CONCLUSIONS
  Based on the clinical and molecular findings, both patients appear to have novel presentations of WSS. As the hallmark hypertrichosis cubiti was not initially appreciated in either case, this syndrome was not suspected during the clinical evaluation. This report expands the phenotypic spectrum of the clinical phenotypes and KMT2A variants associated with WSS.
authors.forename: Samuel P
authors.initials: SP
authors.lastname: Strom
authors.forename: Reymundo
authors.initials: R
authors.lastname: Lozano
authors.forename: Hane
authors.initials: H
authors.lastname: Lee
authors.forename: Naghmeh
authors.initials: N
authors.lastname: Dorrani
authors.forename: John
authors.initials: J
authors.lastname: Mann
authors.forename: Patricia F
authors.initials: PF
authors.lastname: O'Lague
authors.forename: Nicole
authors.initials: N
authors.lastname: Mans
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Deignan
authors.forename: Eric
authors.initials: E
authors.lastname: Vilain
authors.forename: Stanley F
authors.initials: SF
authors.lastname: Nelson
authors.forename: Wayne W
authors.initials: WW
authors.lastname: Grody
authors.affiliation: Clinical Genomics Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA. Fquintero@mednet.ucla.edu.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Quintero-Rivera
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D019295:Computational Biology / Q000379:methods; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics*; D059472:Exome; D019066:Facies; D005260:Female; D014644:Genetic Variation; D059014:High-Throughput Nucleotide Sequencing; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D010641:Phenotype; D013577:Syndrome
chemical_list: C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase