A Study On Association Of IRF6 MAFB ARHGAP29 Ski Gene Variants Analysis Of Microsatellite Polymorphism And The Risk Of Isolated Non Syndromic Cleft Lip And Palate In South Indian Dravidian Population

Abstract

Symmetrical development of the face involves one of the most complex events in embryogenic development, along with gene expressions. The basis of many diseases is the accidental alteration of DNA. Genetic mutations or alterations in an individual s genome, can be inherited, affecting cells that perpetually divide (germ-line mutations), or they occur at any point during a person s life (somatic mutation) 28. Any disturbance in the signalling events of the genes would interfere with normal cellular function. Such alterations which happen during development of face would result in Orofacial clefts and Orofacial deformities80. Cleft lip and palate can appear as an isolated birth defect or can be associated with other malformations. If the cleft lip and palate appear together with a number of other malformations the cleft condition is referred to as Syndromic (SC) whereas when cleft lip and palate appears alone, it is referred to as Non-syndromic (NSC) condition57. In NSC forms, the affected individuals have no other physical or developmental anomalies. newlineThe differences in the frequency of different alleles were statistically significant between non syndromic cleft lip and palate and controls only for RARA microsatellite. Microsatellite from rest of the genes has not shown significant differences between case and controls. Of the patients that were analyzed, none of them carried the reported H131Q mutation including those tested from race matched controls. This indicate that MAFB gene seems to be more population specific. Of the patient that we analyzed, 75% (n = 25) of them carried GTC / GTC homozygous allele that encodes for valine / valine aminoacid relative to GTC / ATC heterzygous allele, Which encodes for valine / isoleucine aminoacids. GTC / TC allele occurred in 25% of (n = 8) of cleft patient while none of them carried isoleucine / isoleucine polymorphism. The occurrence of valine / valine in majority of cases suggests that this genetic polymorphism is transmitted in patients with cleft lip/palate relative to valine /isoleucine carriers. This is consistent with the fact that homozygous GTC / GTC (valine / valine) allele acts as a recessive mutation. Besides, the study also clearly identifies the prevalence of valine / isoleucine polymorphism in cleft patients of tamil speaking dravidian origin. This finding is in contrary to the one reported earlier by Zucchero et al, which identified the occurrence GTC / ATC (valine/ isoleucine) allele to be rare in Indian population. Of the patients that were analyzed, mutation occurred in one cleft lip and palate patient. There was a nucleotide substitution that converted Glutamine to Histamine at position 99(Q99H). The polymorphism in the SKI gene (homozygous state G/G) at intron 4 appears to be significantly associated with the occurrence of cleft lip/palate. Hence, the orthodonist s role is not only limited in aligning the teeth but also being aware of the various factors associated with Cleft lip and palate like folic acid deficiency, vitamin A toxicity, smoking and alcohol intake during pregnancy, etc. Knowledge of the 114 | Page same would help to motivate the parents to reduce the risk in the future through genetic counseling. newline newline