Assessment of candidate genes and genetic heterogeneity in human non syndromic orofacial clefts specifically non syndromic cleft lip with or without palate

Abstract

Non syndromic orofacial clefts specifically non-syndromic cleft lip/palate are one of the most common craniofacial malformation among birth defects in human having multifactorial etiology with an incidence of 1:700/1000. On the basis of association with other congenital malformations or their presence as isolated anomaly, OFC can be classified as syndromic (30%) and nonsyndromic (70%) respectively. The major cause of disease demonstrates complex interplay between genetic and environmental factors. The pathogenic mechanism of underlying factors have been provided by different genetic studies on large-scale with significant recent advances in genotyping technologies usually based on linkage or genome wide association studies (GWAS). On the basis of recent studies, new tools to identify causative genes involved in NSCL/P reported approximately more than 30 genetic risk loci that are responsible for pathogenesis of facial deformation. Despite these findings, it is still uncertain that how much of variance in NSCL/P predisposing factors can be explain by identified risk loci, as they all together accounts for only 20%–25% of NSCL/P heritability. So there is need of further findings about the problem of rare low frequency coding variants and other missing responsive factors or genetic modifiers. This review will described those potential genes and loci reported in different studies whose involvement in pathogenesis of nonsyndromic OFC has wide scientific evidence.

Assessment of the correlation between various risk factors and orofacial cleft disorder spectrum: a retrospective case-control study

“…Orofacial clefts (OFCs) comprise a wide range of malformations, including cleft lip, cleft palate, and cleft lip with cleft palate, which can vary in terms of etiology, severity, and disease burden [1]. The etiology of OFCs is multifactorial, including various genetic (e.g., chromosomal abnormalities and syndromes) and environmental (e.g., medication use, dietary deficiencies, smoking, consumption of alcohol, obesity, exposure to toxins, high altitude, birth order, socioeconomic status, and parental age) factors [2][3][4][5][6]. Therefore, by understanding the multifactorial etiology of these abnormalities, we can explain the proposed approaches for the prevention and treatment of OFCs [7,8].…”

“…Therefore, by understanding the multifactorial etiology of these abnormalities, we can explain the proposed approaches for the prevention and treatment of OFCs [ 7 , 8 ]. Environmental factors, either alone or in combination with genetic factors involved in morphogenesis (e.g., TGF-α/TGF-β, BCL3, and MSX1), are commonly responsible for 60% of OFC abnormalities [ 4 ]. A wide range of pharmaceutical products, such as medications, which are generally used for the treatment of cancer, arthritis, and psoriasis, may also cause OFCs [ 9 ].…”

Condições sociais e clínicas associadas à promoção de saúde em pacientes com fissuras labiopalatais atendidos em um centro de referência

“…Por se tratar de uma doença Genética multifatorial, fatores ambientais podem precipitar o aparecimento das FLP quando há uma predisposição hereditária (4,(19)(20)(21). Portanto, além dos fatores genéticos/hereditários na gênese das FLP, diversos fatores ambientais são considerados de risco para o desenvolvimento desta doença.…”

Analysis of zebrafish periderm enhancers facilitates identification of a regulatory variant near humanKRT8/18

“…Concordance for non-syndromic cleft lip with or without cleft palate (NSCLP) is about 50% in monozygotic twins, suggesting a strong genetic contribution to its etiology 1; 2 . Genome-wide association studies (GWAS) have advanced our understanding of this contribution as multiple independent GWAS, and meta-analyses of them, have identified more than 40 associated loci 3 . However, GWAS methods cannot distinguish SNPs that directly influence risk (i.e., functional SNPs) from those merely in linkage disequilibrium with such SNPs (i.e., rider SNPs).…”