28-05-2025
Genetic study unveils key role of IRF6 gene in orofacial clefts
A genetic research initiative led by the Jubilee Centre for Medical Research (JCMR), Thrissur, has made a significant leap in understanding the genetic underpinnings of orofacial clefts in the Kerala population. Led by Dr. Alex George, Scientist at JCMR, and inspired by the visionary work of the late Dr. H.S. Adenwalla, the study is a comprehensive exploration of the IRF6 gene's role in non-syndromic orofacial clefts (NSOFC) in the State.
The research, conducted in partnership with the Charles Pinto Centre for Cleft Lip, Palate and Craniofacial Anomalies, is funded by Smile Train India. It includes two landmark studies recently published in reputed scientific journals. Both studies reinforce the crucial involvement of the IRF6 gene in the development of orofacial clefts and offer valuable insights into how genetic inheritance can influence susceptibility.
'The first study, published in the February 2025 issue of Archives of Oral Biology, employed an advanced trio-based analysis. This method investigated the inheritance patterns of IRF6 gene variants from parents to children among families affected by non-syndromic cleft lip with or without palate in Kerala,' says Dr. Alex George.
Notably, this research uncovered a significant association of IRF6 polymorphisms with paternal transmission for variant rs2235371 and maternal transmission for rs7552506, providing insights into genetic inheritance patterns that influence susceptibility, he added.
The second study, published in Gene (March 2025), utilised a case-control approach involving five distinct IRF6 single nucleotide polymorphisms (SNPs). This study identified specific genetic markers that are strongly associated with either an increased risk or protective effect against developing orofacial clefts.
'Scientifically, the research sheds light on the complex interplay of gene-by-gene and gene-by-environment interactions, opening doors to personalised genetic screening, early counselling, and potential targeted interventions. For the public, the takeaway is simple: a child's facial development is intricately linked to genetic makeup, and understanding these links is crucial for better healthcare strategies,' Dr Alex George pointed out.
The lead author of the studies Reema Rose Alappat, CSIR-Senior Research Fellow, has made an outstanding contribution through her PhD research. Co-authors include Dr. Narayanan PV (Chief Consultant, HS Adenwalla Institute of Cleft Lip and Palate), Dr. P R Varghese (Research Coordinator and Scientist F, JCMR), and Dr. Sunish Kadayil Sachith (Associate Professor, Maharajas College Ernakulam).
This pioneering research has been funded by Smile Train India and CSIR India, with financial backing exceeding ₹1 crore, demonstrating the potential of local research initiatives to achieve globally relevant healthcare advancements.
These studies symbolise a collective commitment to the Orofacial cleft community deepening global understanding of IRF6 and moving towards a future where such conditions are better understood, prevented, and managed.
