Investigation of genetic factors underlying typical orofacial clefts: mutational screening and copy number variation.
Typical orofacial clefts (OFCs) comprise cleft lip, cleft palate and cleft lip and palate. The complex etiology has been postulated to involve chromosome rearrangements, gene mutations and environmental factors. A group of genes including IRF6, FOXE1, GLI2, MSX2, SKI, SATB2, MSX1 and FGF has been implicated in the etiology of OFCs. Recently, the role of the copy number variations (CNVs) has been studied in genetic defects and diseases. CNVs act by modifying gene expression, disrupting gene sequence or altering gene dosage. The aims of this study were to screen the above-mentioned genes and to investigate CNVs in patients with OFCs. The sample was composed of 23 unrelated individuals who were grouped according to phenotype (associated with other anomalies or isolated) and familial recurrence. New sequence variants in GLI2, MSX1 and FGF8 were detected in patients, but not in their parents, as well as in 200 control chromosomes, indicating that these were rare variants. CNV screening identified new genes that can influence OFC pathogenesis, particularly highlighting TCEB3 and KIF7, that could be further analyzed. The findings of the present study suggest that the mechanism underlying CNV associated with sequence variants may play a role in the etiology of OFC.
Department of Medical Genetics, Faculty of Medical Sciences, University of Campinas, UNICAMP, Campinas, São Paulo, Brazil.
Milena
M
Simioni
Department of Medical Genetics, Faculty of Medical Sciences, University of Campinas, UNICAMP, Campinas, São Paulo, Brazil.
Tânia Kawasaki
TK
Araujo
Clinical Genetics Service, Faculty of Medicine, University Hospital and Genetics Sector, Federal University of Alagoas, Maceió, Alagoas, Brazil.
Isabella Lopes
IL
Monlleo
Department of Medical Genetics, Faculty of Medical Sciences, University of Campinas, UNICAMP, Campinas, São Paulo, Brazil.
Cláudia Vianna
CV
Maurer-Morelli
Department of Medical Genetics, Faculty of Medical Sciences, University of Campinas, UNICAMP, Campinas, São Paulo, Brazil.
Vera Lúcia
VL
Gil-da-Silva-Lopes
D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D056915:DNA Copy Number Variations; D000075065:Elongin; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D016547:Kinesins / Q000235:genetics; D008297:Male; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
C000616397:ELOA protein, human; D000075065:Elongin; C502069:KIF7 protein, human; D020033:Protein Isoforms; D014157:Transcription Factors; D016547:Kinesins