title: Duplication 2p25 in a child with clinical features of CHARGE syndrome.
abstract: CHARGE syndrome is a dominant disorder characterized by ocular colobomata, heart defects, choanal atresia, retardation of growth and development, genital hypoplasia, and ear abnormalities including deafness and vestibular disorders. The majority of individuals with CHARGE have pathogenic variants in the gene encoding CHD7, a chromatin remodeling protein. Here, we present a 15-year-old girl with clinical features of CHARGE syndrome and a de novo 6.5 Mb gain of genomic material at 2p25.3-p25.2. The duplicated region contained 24 genes, including the early and broadly expressed transcription factor gene SOX11. Analysis of 28 other patients with CHARGE showed no SOX11 copy number changes or pathogenic sequence variants. To our knowledge, this child's chromosomal abnormality is unique and represents the first co-occurrence of duplication 2p25 and clinical features of CHARGE syndrome. We compare our patient's phenotype to ten previously published patients with isolated terminal duplication 2p, and elaborate on the clinical diagnosis of CHARGE in the context of atypical genetic findings.
authors: Department of Human Genetics, The University of Michigan, Ann Arbor, Michigan.|Department of the Medical Scientist Training Program, The University of Michigan, Ann Arbor, Michigan.
authors: Ethan D
authors: ED
authors: Sperry
authors: Department of Human Genetics, The University of Michigan, Ann Arbor, Michigan.|Department of Pediatrics and Communicable Diseases, The University of Michigan, Ann Arbor, Michigan.
authors: Jane L
authors: JL
authors: Schuette
authors: Department of Genetics, University of Groningen, University Medical Centre, Groningen, The Netherlands.
authors: Conny M A
authors: CM
authors: van Ravenswaaij-Arts
authors: Department of Otolaryngology-Head and Neck Surgery, The University of Michigan, Ann Arbor, Michigan.
authors: Glenn E
authors: GE
authors: Green
authors: Department of Human Genetics, The University of Michigan, Ann Arbor, Michigan.|Department of the Medical Scientist Training Program, The University of Michigan, Ann Arbor, Michigan.|Department of Pediatrics and Communicable Diseases, The University of Michigan, Ann Arbor, Michigan.
authors: Donna M
authors: DM
authors: Martin
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000503:physiopathology; D058747:CHARGE Syndrome / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D020440:Gene Duplication / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D009154:Mutation; D055751:SOXC Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014314:Trisomy / Q000235:genetics* / Q000503:physiopathology
chemical_list: D004268:DNA-Binding Proteins; C097473:SOX11 protein, human; D055751:SOXC Transcription Factors; D004265:DNA Helicases; C491434:CHD7 protein, human
keywords: CHARGE syndrome; duplication 2p25; gene duplication; trisomy 2p