Current concepts in genetics of nonsyndromic clefts

Abstract

Nonsyndromic cleft lip and palate is a complex genetic disorder with variable phenotype, largely attributed to the interactions of the environment and multiple genes, each potentially having certain effects. Numerous genes have been reported in studies demonstrating associations and/or linkage of the cleft lip and palate phenotypes to alleles of microsatellite markers and single nucleotide polymorphisms within specific genes that regulate transcription factors, growth factors, cell signalling and detoxification metabolisms. Although the studies reporting these observations are compelling, most of them lack statistical power. This review compiles the evidence that supports linkage and associations to the various genetic loci and candidate genes. Whereas significant progress has been made in the field of cleft lip and palate genetics in the past decade, the role of the genes and genetic variations within the numerous candidate genes that have been found to associate with the expression of the orofacial cleft phenotype remain to be determined.

Anatomical patterns of cleft lip and palate deformities among neonates in Mekelle, Tigray, Ethiopia; implication of environmental impact

“…3). Our result here is divergent to widely reported higher left sided unilateral clefts than rightsided CLs [27][28][29]. Majority (40.4%) of CL/P were located bilaterally.…”

Association between genetic variants of reported candidate genes or regions and risk of cleft lip with or without cleft palate in the polish population

“…Current estimates support the hypothesis that as many as 14 possibly interacting genes contribute to CL/P development (Schliekelman and Slatkin,2002). Analyses of candidate loci and genome‐wide linkage scans have shown a wide range of plausible candidate genes or regions for clefts (Carinci et al,2007; Murthy and Bhaskar,2009). However, these genetic findings can explain only a small portion of the genetic component contributing to the pathogenesis of CL/P.…”

“…Genetic screens for nucleotide variants of more than 20 CL/P candidate genes such as MSX1 , FOXE1 , GLI2 , JAG2 , LHX8 , or STAB2 have shown that merely 2 to 6% of the total number of individuals with CL/P have mutations in these genes (Jezewski et al,2003; Vieira et al,2005). In addition, multiple candidate gene association studies have identified polymorphic variants that influence the risk of CL/P (Lidral and Moreno,2005; Murthy and Bhaskar,2009). Nevertheless, levels of etiologic heterogeneity underlying CL/P are a reason of common discrepancies in results obtained across these studies, which were conducted in various populations with different ethnic groups.…”

Developmental profiles of the murine palatal methylome

“…Genetic alterations are thought to contribute to ∼20 to 25% of CP cases (Marazita, ; Lidral and Moreno, ) while environmental factors represent contributing factors in the remaining cases. Analyses of mutations indicate that many of the genes responsible for palate development encode transcription factors, growth and signaling molecules and their receptors, and ECM (extracellular matrix) components (reviewed in Cobourne, ; Murray and Schutte, ; Stanier and Moore, ; Lidral and Moreno, ; Rice, ; Carinci et al, ; Gritli‐Linde, ; Juriloff and Harris, ; Jugessur et al, ; Murthy and Bhaskar, ; Vieira, ; Yu et al, ; Bush and Jiang, ). Several of these genes are members of key signal transduction pathways required for palate development.…”