Non-Homologous End Joining Repair Mechanism-Mediated Deletion of CHD7 Gene in a Patient with Typical CHARGE Syndrome
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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.
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.
참고문헌 (19)
- Blake KD, "CHARGE association: an update and review for the primary pediatrician", Clin Pediatr (Phila), 37, pp.159~173 (1998)
- Verloes A., "Updated diagnostic criteria for CHARGE syndrome: a proposal", Am J Med Genet A, 133A, pp.306~308 (2005)
- Woodage T, "Characterization of the CHD family of proteins", Proc Natl Acad Sci USA, 94, pp.11472~11477 (1997)
- Aramaki M, "Phenotypic spectrum of CHARGE syndrome with CHD7 mutations", J Pediatr, 148, pp.410~414 (2006)
- Zentner GE, "Molecular and phenotypic aspects of CHD7 mutation in CHARGE syndrome", Am J Med Genet A, 152A, pp.674~686 (2010)
- Jongmans MC, "CHARGE syndrome: the phenotypic spectrum of mutations in the CHD7 gene", J Med Genet, 43, pp.306~314 (2006)
- Sanlaville D, "CHARGE syndrome: an update", Eur J Hum Genet, 15, pp.389~399 (2007)
- Janssen N, "Mutation update on the CHD7 gene involved in CHARGE syndrome", Hum Mutat, 33, pp.1149~1160 (2012)
- Lee YW, "Clinical and genetic analysis of the CHD7 gene in Korean patients with CHARGE syndrome", Clin Genet, 75, pp.290~293 (2009)
- Song MH, "CHD7 mutational analysis and clinical considerations for auditory rehabilitation in deaf patients with CHARGE syndrome", PLoS One, 6, pp.e24511~ (2011)
- Cho HJ, "Genetic analysis of the CHD7 gene in Korean patients with CHARGE syndrome", Gene, 517, pp.164~168 (2013)
- 김연경, "Identification of a novel mutation in the CHD7 gene in a patient with CHARGE syndrome", Korean Journal of Pediatrics, 57(1), pp.46~49 (2014), 대한소아과학회
- Hastings PJ, "Mechanisms of change in gene copy number", Nat Rev Genet, 10, pp.551~564 (2009)
- Udaka T, "An Alu retrotransposition-mediated deletion of CHD7 in a patient with CHARGE syndrome", Am J Med Genet A, 143A, pp.721~726 (2007)
- Vatta M, "Evidence for replicative mechanism in a CHD7 rearrangement in a patient with CHARGE syndrome", Am J Med Genet A, 161A, pp.3182~3186 (2013)
- Guirouilh-Barbat J, "Impact of the KU80 pathway on NHEJ-induced genome rearrangements in mammalian cells", Mol Cell, 14, pp.611~623 (2004)
- Roth DB, "Mechanisms of nonhomologous recombination in mammalian cells", Mol Cell Biol, 5, pp.2599~2607 (1985)
- Roth DB, "Oligonucleotide capture during end joining in mammalian cells", Nucleic Acids Res, 19, pp.7201~7205 (1991)
- Little KC, "Genomic DNA is captured and amplified during double-strand break (DSB) repair in human cells", Oncogene, 23, pp.4166~4172 (2004)