title: Non-homologous end joining repair mechanism-mediated deletion of CHD7 gene in a patient with typical CHARGE syndrome.
abstract: CHARGE syndrome MIM #214800 is an autosomal dominant syndrome involving multiple congenital malformations. Clinical symptoms include coloboma, heart defects, choanal atresia, retardation of growth or development, genital hypoplasia, and ear anomalies or deafness. Mutations in the chromodomain helicase DNA binding protein 7 (CHD7) gene have been found in 65-70% of CHARGE syndrome patients. Here, we describe a 16-month-old boy with typical CHARGE syndrome, who was referred for CHD7 gene analysis. Sequence analysis and multiplex ligation-dependent probe amplification were performed. A heterozygous 38,304-bp deletion encompassing exon 3 with a 4-bp insertion was identified. There were no Alu sequences adjacent to the breakpoints, and no sequence microhomology was observed at the junction. Therefore, this large deletion may have been mediated by non-homologous end joining. The mechanism of the deletion in the current case differs from the previously suggested mechanisms underlying large deletions or complex genomic rearrangements in the CHD7 gene, and this is the first report of CHD7 deletion by this mechanism worldwide.
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Jong Hee
authors.initials: JH
authors.lastname: Chae
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Jung Ae
authors.initials: JA
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Sung Im
authors.initials: SI
authors.lastname: Cho
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Seo
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Hyunwoong
authors.initials: H
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Moon-Woo
authors.initials: MW
authors.lastname: Seong
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Sung Sup
authors.initials: SS
authors.lastname: Park
mesh_terms: D020087:Alu Elements / Q000235:genetics; D001483:Base Sequence; D058747:CHARGE Syndrome / Q000175:diagnosis / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D059766:DNA End-Joining Repair; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D018628:Gene Dosage; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion
chemical_list: D004268:DNA-Binding Proteins; D004247:DNA; D004265:DNA Helicases; C491434:CHD7 protein, human
keywords: CHARGE syndrome; CHD7; Large deletion; Non-homologous end joining