RESUMEN
Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a common craniofacial anomaly with a complex and heterogeneous aetiology. Knowledge regarding specific genetic factors underlying this birth defect is still not well understood. Therefore, we conducted an independent replication analysis for the top-associated variants located within the DLG1 locus at chromosome 3q29, which was identified as a novel cleft-susceptibility locus in our genome-wide association study (GWAS). Mega-analysis of the pooled individual data from the GWAS and replication study confirmed that common DLG1 variants are associated with the risk of nsCL/P. Two single nucleotide polymorphisms (SNPs), rs338217 and rs7649443, were statistically significant even at the genome-wide level (Ptrend = 9.70E-10 and Ptrend = 8.96E-09, respectively). Three other SNPs, rs9826379, rs6805920 and rs6583202, reached a suggestive genome-wide significance threshold (Ptrend < 1.00E-05). The location of the strongest individual SNP in the intronic sequence of the gene encoding DLG1 antisense RNA suggests that the true causal variant implicated in the risk of nsCL/P may affect the DLG1 gene expression level rather than structure of the encoded protein. In conclusion, we identified a novel cleft-susceptibility locus at chromosome 3q29 with a DLG1 as a novel candidate gene for this common craniofacial anomaly.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Encéfalo/anomalías , Labio Leporino/genética , Fisura del Paladar/genética , Proteínas de la Membrana/genética , Encéfalo/patología , Labio Leporino/patología , Fisura del Paladar/patología , Homólogo 1 de la Proteína Discs Large , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Between 1976 and 2002, 272 ear reconstructions were performed in our unit using the methods of Tanzer (n=38), Brent (n=156) and Nagata (n=78). We present this experience and our modifications of these methods, and describe our current practice.