Progress toward discerning the genetics of cleft lip.
OBJECTIVE
Orofacial clefts are common birth defects with a known genetic component to their etiology. Most orofacial clefts are nonsyndromic, isolated defects, which can be separated into two different phenotypes: (1) cleft lip with or without cleft palate and (2) cleft palate only. Both are genetically complex traits, which has limited the ability to identify disease loci or genes. The purpose of this review is to summarize recent progress of human genetic studies in identifying causal genes for isolated or nonsyndromic cleft lip with or without cleft palate.


RESULTS
The results of multiple genome scans and a subsequent meta-analysis have significantly advanced our knowledge by revealing novel loci. Furthermore, candidate gene approaches have identified important roles for IRF6 and MSX1. To date, causal mutations with a known functional effect have not yet been described.


CONCLUSIONS
With the implementation of genome-wide association studies and inexpensive sequencing, future studies will identify disease genes and characterize both gene-environment and gene-gene interactions to provide knowledge for risk counseling and the development of preventive therapies.
Lidral
Andrew C
AC
Department of Orthodontics, University of Iowa, Iowa City, Iowa 52242, USA. Andrew-Lidral@uiowa.edu
Moreno
Lina M
LM
D000081242:B-Cell Lymphoma 3 Protein; D002648:Child; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics; D051957:MSX1 Transcription Factor / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D014157:Transcription Factors; D016212:Transforming Growth Factor beta / Q000235:genetics; D053782:Transforming Growth Factor beta3
D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; C109803:IRF6 protein, human; D050835:Interferon Regulatory Factors; D051957:MSX1 Transcription Factor; C484083:MSX1 protein, human; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3