Association study of five mutation in FGFR1 and FGFR2 genes in Indian children with craniosynostosis

摘要

Background: Craniosynostosis is one the major genetic disorder in children and it occurs in 1 per 2,200 live births. It may be define as abnormal premature fusion of the cranial sutures bones in children. Several causes have been reported that may have a possible role in the development of the disorder. Fibrinogen growth Factor 1(FGFR1) & fibroblast growth factor receptor 2 (FGFR2) show a vital role in developing the craniosynostosis in western population’s children but from India no report is available. The aim of this study was to investigate the association between mutation of FGFR1 and FGFR2 (IIIa and IIIb) genes with syndromic as well as non-syndromic craniosynostosis in Indian population. Methods: Retrospective analysis of our records from January 2008 to December 2012 was done. A total of Sixty three children (along with their parents) with craniosynostosis and Fifty one children with No-craniosynostosis (healthy school going children) attending the Monday out Patient Door (OPD) facility of the department of Paediatric Surgery, All India Institute of Medical Sciences (AIIMSs), Delhi, India were considered for the study. A restriction fragment length polymorphism (RFLP) polymerase chain reaction (PCR) was carried out for genotyping Fibrinogen growth Factor 1 (FGFR1) & fibroblast growth factor receptor 2 (FGFR2) mutations in all the participants. Results: There were 33 (80.4%) nonsyndromic cases of craniosynostosis while 8 (19.5%) were syndromic. Out of these 8 syndromic cases, 4 were Apert syndrome, 3 were Crouzon syndrome and 1 Pfeiffer syndrome. Phenotypically the most common nonsyndromic craniosynostosis was scaphocephaly (19, 57.7%) followed by plagiocephaly in (14, 42.3%). FGFR1 mutation (Pro252Arg) was seen in 1 (2.4%) case of nonsyndromic craniosynostosis while no association was noted either with FGFR1 or with FGFR2 (IIIa & IIIc) mutation in syndromic cases. None of the control group showed any mutation. Conclusion: Our study provides the strongest evidence that association of mutation of FGFR1, FGFR2 (IIIa & IIIb) with syndromic as well as nonsyndromic craniosynostosis does not exist in Indian population as seen in western population.