Revealing the function of a novel splice-site mutation of CHD7 in CHARGE syndrome


Lee B., Duz M. B., Sagong B., Koparir A., Lee K., Choi J. Y., ...Daha Fazla

GENE, cilt.576, sa.2, ss.776-781, 2016 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 576 Sayı: 2
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1016/j.gene.2015.11.006
  • Dergi Adı: GENE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.776-781
  • Anahtar Kelimeler: CHARGE syndrome, CHD7, Splice-site mutation, Frameshift mutation, Turkish, CHROMATIN REMODELING FACTOR, PHENOTYPIC SPECTRUM, DNA-BINDING, GENE, TRANSCRIPTION, COMPLEX, CHROMODOMAINS, REPLICATION, DEFECTS, MICE
  • Kocaeli Üniversitesi Adresli: Hayır

Özet

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. (C) 2015 Elsevier B.V. All rights reserved.