title: Characterization of two novel FANCG mutations in Indian Fanconi anemia patients.
abstract: FA is a rare recessive genetic disorder with autosomal or X-linked mode of inheritance and is associated with 19 different FA complementation groups. We have studied three patients clinically diagnosed as FA. All three patients showed a high frequency chromosomal breakage in MMC induced blood cultures and FANCD2 non-monoubiquitination by western blotting. The molecular analysis using direct sequencing revealed two novel mutations in FANCG; 2 novel mutations c.1143+5G>C and c.883dupG, and a reported mutation c.1471_1473delAAAinsG. We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. All three mutations are potential pathogenic molecular changes which can affect FANCG interactions required for FA pathway, homologous recombination repairs and unhooking step of the ICL repair process.
authors.affiliation: Department of Cytogenetics, 13th Floor, National Institute of Immuno Haematology, KEM Hospital Campus, Parel, Mumbai - 400 012, Maharashtra, India.
authors.forename: Avani
authors.initials: A
authors.lastname: Solanki
authors.affiliation: School of Biotechnology and Bioinformatics, Level 5, D.Y. Patil University, Sector 15, Plot No. 50, CBD Belapur, Navi Mumbai 400 614, Maharashtra, India.
authors.forename: C
authors.initials: C
authors.lastname: Kumar Selvaa
authors.affiliation: Genetics Centre, Institute of Human Genetics, FRIGE House, Jodhpur Village Road, Satellite, Ahmedabad 380 015, Gujarat, India.
authors.forename: Frenny
authors.initials: F
authors.lastname: Sheth
authors.affiliation: Pediatrics Department, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, Delhi 110060, India.
authors.forename: Nita
authors.initials: N
authors.lastname: Radhakrishnan
authors.affiliation: Cancer Care Institute, Indraprastha Apollo Hospital, Sarita Vihar, Delhi Mathura Road, New Delhi - 110076, India.
authors.forename: Manas
authors.initials: M
authors.lastname: Kalra
authors.affiliation: Department of Cytogenetics, 13th Floor, National Institute of Immuno Haematology, KEM Hospital Campus, Parel, Mumbai - 400 012, Maharashtra, India. Electronic address: vbaburao@hotmail.com.
authors.forename: Babu Rao
authors.initials: BR
authors.lastname: Vundinti
mesh_terms: D000595:Amino Acid Sequence; D002648:Child; D019457:Chromosome Breakage; D019295:Computational Biology; D005199:Fanconi Anemia / Q000235:genetics*; D052241:Fanconi Anemia Complementation Group G Protein / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D009154:Mutation; D011487:Protein Conformation
chemical_list: C499909:FANCG protein, human; D052241:Fanconi Anemia Complementation Group G Protein
keywords: Bone marrow failure; Chromosomal breakage; Direct sequencing; FA-G complementation group; FANCD2 monoubiquitination; FANCG; Fanconi anemia