title: Revealing the function of a novel splice-site mutation of CHD7 in CHARGE syndrome.
abstract: Most cases of CHARGE syndrome are sporadic and autosomal dominant. CHD7 is a major causative gene of CHARGE syndrome. In this study, we screened CHD7 in two Turkish patients demonstrating symptoms of CHARGE syndrome such as coloboma, heart defect, choanal atresia, retarded growth, genital abnomalities and ear anomalies. Two mutations of CHD7 were identified including a novel splice-site mutation (c.2443-2A>G) and a previously known frameshift mutation (c.2504_2508delATCTT). We performed exon trapping analysis to determine the effect of the c.2443-2A>G mutation at the transcriptional level, and found that it caused a complete skip of exon 7 and splicing at a cryptic splice acceptor site. Our current study is the second study demonstrating an exon 7 deficit in CHD7. Results of previous studies suggest that the c.2443-2A>G mutation affects the formation of nasal tissues and the neural retina during early development, resulting in choanal atresia and coloboma, respectively. The findings of the present study will improve our understanding of the genetic causes of CHARGE syndrome.
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, South Korea; School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, South Korea.
authors.forename: Byeonghyeon
authors.initials: B
authors.lastname: Lee
authors.affiliation: Department of Medical Genetics, Istanbul University Cerrahpasa Medical School, Istanbul, Turkey.
authors.forename: Mehmet Bugrahan
authors.initials: MB
authors.lastname: Duz
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, South Korea; School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, South Korea.
authors.forename: Borum
authors.initials: B
authors.lastname: Sagong
authors.affiliation: Department of Medical Genetics, Istanbul University Cerrahpasa Medical School, Istanbul, Turkey.
authors.forename: Asuman
authors.initials: A
authors.lastname: Koparir
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, Kyungpook National University, Daegu, South Korea.
authors.forename: Kyu-Yup
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Department of Medical Genetics, Istanbul University Cerrahpasa Medical School, Istanbul, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Seven
authors.affiliation: Department of Medical Genetics, Biruni University Medical School, Istanbul, Turkey.
authors.forename: Adnan
authors.initials: A
authors.lastname: Yuksel
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, South Korea; School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, South Korea. Electronic address: kimuk@knu.ac.kr.
authors.forename: Un-Kyung
authors.initials: UK
authors.lastname: Kim
authors.affiliation: Department of Medical Genetics, Istanbul University Cerrahpasa Medical School, Istanbul, Turkey; Department of Medical Genetics, Biruni University Medical School, Istanbul, Turkey; Department of Pathology & Immunology, Baylor College of Medicine, Michael E. DeBakey VAMC, Houston, TX, United States. Electronic address: mozen@bcm.edu.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Ozen
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D058747:CHARGE Syndrome / Q000235:genetics*; D002675:Child, Preschool; D004265:DNA Helicases / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D022821:RNA Splice Sites / Q000235:genetics*; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; D022821:RNA Splice Sites; D004265:DNA Helicases; C491434:CHD7 protein, human
keywords: CHARGE syndrome; CHD7; Frameshift mutation; Splice-site mutation; Turkish