RESUMEN
BACKGROUND: Mandatory fortification with folic acid (FA) was implemented in Chile in 2000. Thereafter, the rate of spina bifida decreased by 52 to 55%. Genetic abnormalities in folate metabolism may be involved in the etiology of spina bifida. AIM: To evaluate the association between myelomeningocele (MM) and c.A1298C and c.C677T polymorphisms within the coding gene for 5,10-methylenetetrahydrofolate reductase (MTHFR) in the Chilean population. MATERIAL AND METHODS: These polymorphisms were genotyped in 105 patients showing isolated MM, born after the onset of FA fortification, and in their parents. The transmission disequilibrium test (TDT) was performed to evaluate alterations in the transmission of both alleles and haplotypes MTHFR polymorphism. We also evaluated the presence of parent-origin-effect (POE) of alleles using the Clayton's extension of the TDT. RESULTS: TDT analysis showed no significant distortions in the transmission of alleles or haplotypes. Moreover, although the POE showed increased risk for maternally derived allele, this risk was not statistically significant. CONCLUSIONS: The studied variants in the MTHFR gene (c.C677T and c.A1298C) do not constitute risk factors for MM in this sample of Chilean patients and their parents.
Asunto(s)
Meningomielocele/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo Genético/genética , Disrafia Espinal/genética , Niño , Preescolar , Chile , Femenino , Frecuencia de los Genes , Genotipo , Haplotipos , Humanos , Lactante , Masculino , Meningomielocele/enzimología , Factores de Riesgo , Disrafia Espinal/enzimologíaRESUMEN
Obese/diabetic mothers present a higher risk to develop offspring with myelomeningocele (MM), evidence supporting the role of energy homeostasis-related genes in neural tube defects. Using polymerase chain reaction-restriction fragment length polymorphism, we have genotyped SLC2A1, HK1, and LEPR single-nucleotide polymorphisms in 105 Chilean patients with MM and their parents in order to evaluate allele-phenotype associations by means of allele/haplotype transmission test (TDT) and parent-of-origin effects. We detected an undertransmission for the SLC2A1 haplotype T-A (rs710218-rs2229682; P = .040), which was not significant when only lower MM (90% of the cases) was analyzed. In addition, the leptin receptor rs1137100 G allele showed a significant increase in the risk of MM for maternal-derived alleles in the whole sample (2.43-fold; P = .038) and in lower MM (3.20-fold; P = .014). Our results support the role of genes involved in energy homeostasis in the risk of developing MM, thus sustaining the hypothesis of diverse pathways and genetic mechanisms acting in the expression of such birth defect.
Asunto(s)
Alelos , Transportador de Glucosa de Tipo 1/genética , Hexoquinasa/genética , Meningomielocele/genética , Polimorfismo Genético/genética , Receptores de Leptina/genética , Niño , Preescolar , Chile/epidemiología , Femenino , Estudios de Asociación Genética/métodos , Humanos , Lactante , Masculino , Meningomielocele/epidemiología , PadresRESUMEN
Background: Mandatory fortification with folic acid (FA) was implemented in Chile in 2000. Thereafter, the rate of spina bifida decreased by 52 to 55%. Genetic abnormalities in folate metabolism may be involved in the etiology of spina bifida. Aim: To evaluate the association between myelomeningocele (MM) and c.A1298C and c.C677T polymorphisms within the coding gene for 5,10-methylenetetrahydrofolate reductase (MTHFR) in the Chilean population. Material and Methods: These polymorphisms were genotyped in 105 patients showing isolated MM, born after the onset of FA fortification, and in their parents. The transmission disequilibrium test (TDT) was performed to evaluate alterations in the transmission of both alleles and haplotypes MTHFR polymorphism. We also evaluated the presence of parent-origin-effect (POE) of alleles using the Clayton’s extension of the TDT. Results: TDT analysis showed no significant distortions in the transmission of alleles or haplotypes. Moreover, although the POE showed increased risk for maternally derived allele, this risk was not statistically significant. Conclusions: The studied variants in the MTHFR gene (c.C677T and c.A1298C) do not constitute risk factors for MM in this sample of Chilean patients and their parents.
Asunto(s)
Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Meningomielocele/genética , /genética , Polimorfismo Genético/genética , Disrafia Espinal/genética , Chile , Frecuencia de los Genes , Genotipo , Haplotipos , Meningomielocele/enzimología , Factores de Riesgo , Disrafia Espinal/enzimologíaRESUMEN
El síndrome Proteus es una hamartosis congénita, aparentemente poco frecuente, delineada recientemente. Se describen dos casos, uno con un fenotipo grave y característico, incluyendo retardo mental, y otro con asimetria moderada, macrodactilia y anomalías pulmonares quísticas graves. Estos casos corroboran la característica "polimórfica" de este síndrome. Basado en estos dos pacientes y en los trece publicados en el mundo, se analiza su fenotipo y aspectos más relevantes