Estudio de asociación por desequilibrio de ligamiento entre los genes TGFA, RARA, y BCL3 y fisura labiopalatina no sindrómica (FLPNS) en la población chilena / Possible association due to linkage disequilibrium of TGFA, RARA and BCL3 with nonsyndromic cleft lip with or without cleft palate in the Chilean population

Background: Nonsyndromic cleft lip/palate (NSCLP) is a congenital malformation with the characteristics of a complex genetic trait. Based on experimental evidences as well as on association and linkage studies candidate genes TGFA, RARA and BCL3 have been postulated as being involved in the genetic etiology of this pathology. Aim: To test the possible association due to linkage disequilibrium between microsatellite markers located at less than 1cM from the three candidate genes and nonsyndromic cleft lip/palate using the case-parents trio design. Patients and Methods: The sample consisted of 58 case-parents trios. Two microsatellite markers, flanking each one of the candidate genes were analyzed by means of the polymerase chain reaction (PCR) with fluorescent labeled microsatellite markers. Electrophoresis of the PCR products was performed on a laser-fluorescent automatic DNA sequencer. Nonparametric ETDT was used to analyze the genotype data. Results: Significant linkage disequilibrium was detected between D2S443 (TGFA) and NSCLP. Significance was almost reached between D17S800 (RARA) and NSCLP. Alleles 239bp (D2S443) and 172bp (D17S800) showed significant preferential transmission from heterozygous parents to affected offspring. In the case of BCL3 both markers showed no significant results. Conclusions: The results of the present study do not show clear evidence that TGFA or RARA could be involved in the genetic etiology of NSCLP. Even though the importance of retinoic acid in the development of the embryo is well documented the results obtained for RARA are difficult to analyze. In relation to the possible role of BCL3 in NSCLP, recent information postulates that other genes located in the same chromosome region could be involved in NSCLP.

Síndrome con defectos radiales, labio leporino complicado y ectrodactilia / Familial complicated cleft palate radial defects and ectrodactily

Se presenta una familia formada por 15 miembros, de los cuales 10 son consanguíneos portadores de una asociación de defecto radial, labio leporino complicado y ectrodactilia, lo que se hereda en forma autosómica dominante con penetrancia incompleta y expresividad variable. Se postula una alteración génica a nivel de genes que actúan durante el período embrionario