@article {290,
	title = {Evidence for replicative mechanism in a CHD7 rearrangement in a patient with CHARGE syndrome.},
	journal = {Am J Med Genet A},
	volume = {161A},
	year = {2013},
	month = {2013 Dec},
	pages = {3182-6},
	abstract = {<p>Haploinsufficiency of CHD7 (OMIM$\#$ 608892) is known to cause CHARGE syndrome (OMIM$\#$ 214800). Molecular testing supports a definitive diagnosis in approximately 65-70\% of cases. Most CHD7 mutations arise de novo, and no mutations affecting exon-7 have been reported to date. We report on an 8-year-old girl diagnosed with CHARGE syndrome that was referred to our laboratory for comprehensive CHD7 gene screening. Genomic DNA from the subject with a suspected diagnosis of CHARGE was isolated from peripheral blood lymphocytes and comprehensive Sanger sequencing, along with deletion/duplication analysis of the CHD7 gene using multiplex ligation-dependent probe amplification (MLPA), was performed. MLPA analysis identified a reduced single probe signal for exon-7 of the CHD7 gene consistent with potential heterozygous deletion. Long-range PCR breakpoint analysis identified a complex genomic rearrangement (CGR) leading to the deletion of exon-7 and breakpoints consistent with a replicative mechanism such as fork stalling and template switching (FoSTeS) or microhomology-mediated break-induced replication (MMBIR). Taken together this represents the first evidence for a CHD7 intragenic CGR in a patient with CHARGE syndrome leading to what appears to be also the first report of a mutation specifically disrupting exon-7. Although likely rare, CGR may represent an overlooked mechanism in subjects with CHARGE syndrome that can be missed by current sequencing and dosage assays.</p>},
	keywords = {Abnormalities, Multiple, CHARGE Syndrome, Child, DNA Helicases, DNA Replication, DNA-Binding Proteins, Exons, Female, Gene Deletion, Haploinsufficiency, Humans, Mutation},
	issn = {1552-4833},
	doi = {10.1002/ajmg.a.36178},
	author = {Vatta, Matteo and Niu, Zhiyv and Lupski, James R and Putnam, Philip and Spoonamore, Katherine G and Fang, Ping and Eng, Christine M and Willis, Alecia S}
}
