title: A characteristic syndrome associated with microduplication of 8q12, inclusive of CHD7.
abstract: This report describes a 4 year-old girl with history of hypotonia, developmental delay, and failure to thrive in infancy. She has cognitive impairment and multiple congenital anomalies, including Duane anomaly, Mondini malformation with associated deafness, external ear malformations, and atrial and ventricular septal defects. Array comparative genomic hybridization demonstrated a de novo tandem 6.9 Mb duplication of at least 15 genes in chromosome 8q12, inclusive of CHD7, with breakpoints at 58,388,614 bp and 65,306,097 bp (NCBI build 36.1). Loss of CHD7 by microdeletion or intragenic mutation causes CHARGE syndrome. There is one previous report of an individual with microduplication of 8q12 involving CHD7. He also had early hypotonia, cognitive impairment, Duane anomaly, sensorineural deafness and a congenital heart defect. This rather specific recurrent pattern of congenital anomalies associated with overlapping duplications of the genomic region containing CHD7 suggests that the phenotype in these two patients may be the result of abnormal CHD7 dosage.
authors.affiliation: Department of Medical Genetics, University of British Columbia, Canada.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Lehman
authors.forename: Jan M
authors.initials: JM
authors.lastname: Friedman
authors.forename: David
authors.initials: D
authors.lastname: Chai
authors.forename: Farah R
authors.initials: FR
authors.lastname: Zahir
authors.forename: Marco A
authors.initials: MA
authors.lastname: Marra
authors.forename: Larraine
authors.initials: L
authors.lastname: Prisman
authors.forename: Erica
authors.initials: E
authors.lastname: Tsang
authors.forename: Patrice
authors.initials: P
authors.lastname: Eydoux
authors.forename: Linlea
authors.initials: L
authors.lastname: Armstrong
mesh_terms: D002675:Child, Preschool; D002869:Chromosome Aberrations; D002898:Chromosomes, Human, Pair 8; D004265:DNA Helicases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D020641:Polymorphism, Single Nucleotide
chemical_list: D004268:DNA-Binding Proteins; D004265:DNA Helicases; C491434:CHD7 protein, human