Three Novel Mutations of CHD7 Gene in Two Turkish Patients with Charge Syndrome; A Double Point Mutation and an Insertion

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Abstract

The CHARGE (coloboma, heart defects, atresia, retardation, genital, ear) syndrome is a genetic disease characterized by ocular coloboma, choanal atresia or stenosis and semicircular canal abnormalities. Most of the patients clinically diagnosed with CHARGE syndrome have mutations in chromodomain helicase DNA-binding protein 7 (CHD7) gene. The CHD7 gene is located on chromosome 8q12.1, and up to now, there are more than 500 pathogenic mutations identified in the literature. We report two patients diagnosed with CHARGE syndrome with two novel mutations in the CHD7 gene: the first patient has double consecutive novel mutations in three adjacent codons, and the other has a novel insertion.

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  • 1. Burkitt Wright EMM O’Connor R Kerr BA. Radial aplasia in CHARGE syndrome: a new association. Eur J Med Genet. 2009; 52(4): 239-241.

  • 2. Koletzko B Majewski F Congenital anomalies in patients with choanal atresia: CHARGE-association. Eur J Pediatr. 1984; 142(4): 271-275.

  • 3. Kim HG Kurth I Lan F Meliciani I Wenzel W Eom SH et al. Mutations in CHD7 encoding a chromatin-remodeling protein cause idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Am J Hum Genet. 2008; 83(4): 511-519.

  • 4. Vervloed MPJ Hoevenaars-van den Boom MAA Knoors H van Ravenswaaij CMA Admiraal RJC. CHARGE syndrome: Relations between behavioral characteristics and medical conditions. Am J Med Genet. 2006; 140A(8): 851-862.

  • 5. Graham JM. A recognizable syndrome within CHARGE association: Hall-Hittner syndrome. Am J Med Genet. 2001; 99(2): 120-123.

  • 6. Hsu P Ma A Wilson M Williams G Curotta J Munns CF et al. CHARGE syndrome: a review. J Paediatr Child Health. 2014; 50(7): 504-511.

  • 7. Bajpai R Chen DA Rada-Iglesias A Zhang J Xiong Y Helms J (see above) et al. CHD7 cooperates with PBAF to control multipotent neural crest formation. Nature. 2010; 463(7283): 958-62.

  • 8. Green GE Huq FS Emery SB Mukherji SK Martin DM. CHD7 muttions and CHARGE syndrome in semicircular canal dysplasia. Otol Neurotol. 2014; 35(8): 1466-1470.

  • 9. Vatta M Niu Z Lupski JR Putnam P Spoonamore KG Fang P et al. Evidence for replicative mechanism in a CHD7 rearrangement in a patient with CHARGE syndrome. Am J Med Genet A. 2013; 161A(12): 3182-3186.

  • 10. Janssen N Bergman JE Swertz MA Tranebjaerg L Lodahl M Schoots J et al. Mutation update on the CHD7 gene involved in CHARGE syndrome. Hum Mutat. 2012; 33(8): 1149-1160.

  • 11. Verloes A. Updated diagnostic criteria for CHARGE syndrome: aproposal. Am J Med Genet A. 2005; 133A(3): 306-308.

  • 12. Issekutz KA Graham JM Jr Prasad C Smith IM Blake KD. An epidemiological analysis of CHARGE syndrome: Preliminary results from a Canadian study. Am J Med Genet A. 2005; 133A(3): 309-317.

  • 13. Wessels K Bohnhorst B Luhmer I Morlot S Bohring A Jonasson J et al. Novel CHD7 mutations contributing to the mutation spectrum in patients with CHARGE syndrome. Eur J Med Genet. 2010; 53(5): 280-285.

  • 14. Mitchell JA Giangiacomo J Hefner MA Thelin JW Pickens JM. Dominant CHARGE association. Ophthalmic Paediatr Genet. 1985; 6(1-2): 271-276.

  • 15. Martinez-Quintana E Rodriguez-Gonzalez F Garay-Sanchez P Tugores A. Novel frameshift CHD7 mutation related to CHARGE syndrome. Mol Syndromol. 2014; 5(1): 36-40.

  • 16. Lalani SR Safiullah AM Fernbach SD Harutyunyan KG Thaller C Peterson LE et al. Spec trum of CHD7 mutations in 110 individuals with CHARGE syndrome and genotype-phenotype correlation. Am J Hum Genet. 2006; 78(2): 303-314.

  • 17. Aramaki M Udaka T Kosaki R Makita Y Okamoto N Yoshihashi H et al. Phenotypic spectrum of CHARGE syndrome with CHD7 mutations. J Pediatr. 2006; 148(3): 410-414.

  • 18. Blake KD Davenport SL Hall BD Hefner MA Pagon RA Williams MS et al. CHARGE association: An update and review for the primary pediatrician. Clin Pediatr. 1998; 37(3): 159-173.

  • 19. Saladi SV de la Serna IL. ATP dependent chromatin remodeling enzymes in emryonic stem cells. Stem Cell Rev. 2010; 6(1): 62-73.

  • 20. Bosman EA Penn AC Ambrose JC Kettleborough R Stemple DL Steel KP. Multiple mutations in mouse Chd7 provide models for CHARGE syndrome. Hum Mol Genet. 2005; 14(22): 3463-3476.

  • 21. Bouazoune K Kingston RE. Chromatin remodeling by the CHD7 protein is impaired by mutations that cause human developmental disorders. Proc Natl Acad Sci USA. 2012; 109(47): 19238-19243.

  • 22. Vuorela P Ala-Mello S Saloranta C Penttinen M Pöyhönen M Huoponen K et al. Molecular analysis of the CHD7 gene in CHARGE syndrome: Identification of 22 novel mutations and evidence for a low contribution of large CHD7 deletions. Genet Med. 2007; 9(10): 690-694.

  • 23. Chen JM Férec C Cooper DN. Patterns and mutational signatures of tandem base substitutions causing human inherited disease. Hum Mutat. 2013; 34(8): 1119-1130.

  • 24. Chen JM1 Férec C Cooper DN. Transient hypermutability chromothripsis and replication-based mechanisms in the generation of concurrent clustered mutations. Mutat Res. 2012; 750(1): 52-59.

  • 25. Johnson D Morrison N Grant L Turner T Fantes J Connor JM et al. Confirmation of CHD7 as a cause of CHARGE association identified by mapping a balanced chromosome translocation in affected monozygotic twins. J Med Genet. 2006; 43(3): 280-284.

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