RESUMO
BACKGROUND: Accumulating evidence indicates that alterations in the serotonin system are related to changes in eating behavior. The serotonin transporter is encoded by the SLC6A4 gene and has been an interesting candidate for anorexia nervosa- restrictive type (AN-R) and bulimia nervosa (BN). Interestingly, functional variants have been identified in the coding region that could contribute to understand the role of this gene in eating disorders. The aim was to identify genetic variants in five exons of SLC6A4 gene using Sanger-sequencing in anorexia nervosa-restrictive and bulimia nervosa patients, and a control group. METHOD: The sample consisted of 86 patients and 50 control subjects. We obtained DNA samples from all subjects and performed Sanger-sequence analysis of the 1, 2, 3, 8 and 9 exons. The sequences were compared with the reference sequence of the SLC6A4 gene. RESULTS: The sequence analysis of the five exons of the gene identified several variants. In the AN-R, we observed two novel variants (g.130delA and c.1740G > A), three synonymous variants (rs57172732, rs55908624, rs74478645) and a missense variant (L90F) reporting a probably deleterious and damaging variant. In BN, we identified two novel variants (g.295C > G and c.1725G > A), and the non-synonymous (rs28914832/I425V), reported as benign. Interestingly, we observed the 425V variant in three patients in the BN, variant that previously was reported in patients with a spectrum obsessive-compulsive disorder. CONCLUSION: The results of our study suggest that variants of the SLC6A4 gene are related with a possible damaging or gain-of-function and may be involved in the susceptibility to AN-R and BN patients. However, the present findings should be considered as preliminary until replicated in large samples.
Assuntos
Anorexia Nervosa/genética , Bulimia Nervosa/genética , Éxons , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Adolescente , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Adulto JovemRESUMO
RESUMEN Objetivos: el objetivo principal del estudio fue evaluar la supervivencia global en pacientes con carcinoma colorrectal metastásico (CCRm) cuyos tumores tuvieran el gen KRAS mutado frente al no mutado. Materiales y métodos: se analizaron los datos de las historias clínicas de pacientes con CCRm (enero 2010 - diciembre 2013) de diferentes hospitales de Lima Metropolitana, cuyos tumores tuvieron evaluación del estado mutacional del exón 2, gen KRAS. Se usaron la curva de supervivencia de Kaplan-Meier y la prueba de long rank o Breslow para las comparaciones de las curvas de supervivencia. Resultados: de los 320 casos analizados, hubo 227 pacientes (70,93%) con KRAS no mutado y 93 (29,07%) con KRAS mutado. La supervivencia global de pacientes con CCRm y KRAS mutado fue mayor que los pacientes con KRAS no mutado (hazart ratio: 0,73; IC 95% 0,55 - 0,98; p=0,037). Conclusión: la población con CCRm y KRAS mutado estudiada en centros médicos de Lima Metropolitana tuvo una supervivencia mayor, comparada con la no mutada, comportamiento diferente a lo encontrado en la literatura mundial.
ABSTRACT Objectives : The main goal for this study was to evaluate overall survival in mCRC patients with mutated vs. wild type KRAS gene (exon 2) status. Materials and Methods : Between January 2010 and December 2013, data from clinical records of mCRC patients from different hospitals in Lima, stating an assessment of the KRAS gene mutation status (exon 2), were analyzed. Kaplan-Meier survival estimates and Log-Rank or Breslow Test were used to compare the survival curves. Results : Three-hundred and twenty cases were analyzed. There were 227 patients (70.93%) with wild type KRAS and 93 (29.07%) with mutated KRAS. The overall survival of mCRC patients and mutated KRAS was higher than that of patients with wild type KRAS (HR: 0.73; 95% CI: 0.55-0.98; P= 0.037). Conclusion : Patients with mCRC and mutated KRAS who were studied in Lima have higher survival rates compared to wild type patients, being this different from what is found in the world literature.
RESUMO
BACKGROUND: Previously, we reported a rare X-linked disorder, Uruguay syndrome in a single family. The main features are pugilistic facies, skeletal deformities, and muscular hypertrophy despite a lack of exercise and cardiac ventricular hypertrophy leading to premature death. METHODS AND RESULTS: An ≈19 Mb critical region on X chromosome was identified through identity-by-descent analysis of 3 affected males. Exome sequencing was conducted on one affected male to identify the disease-causing gene and variant. A splice site variant (c.502-2A>G) in the FHL1 gene was highly suspicious among other candidate genes and variants. FHL1A is the predominant isoform of FHL1 in cardiac and skeletal muscle. Sequencing cDNA showed the splice site variant led to skipping of exons 6 of the FHL1A isoform, equivalent to the FHL1C isoform. Targeted analysis showed that this splice site variant cosegregated with disease in the family. Western blot and immunohistochemical analysis of muscle from the proband showed a significant decrease in protein expression of FHL1A. Real-time polymerase chain reaction analysis of different isoforms of FHL1 demonstrated that the FHL1C is markedly increased. CONCLUSIONS: Mutations in the FHL1 gene have been reported in disorders with skeletal and cardiac myopathy but none has the skeletal or facial phenotype seen in patients with Uruguay syndrome. Our data suggest that a novel FHL1 splice site variant results in the absence of FHL1A and the abundance of FHL1C, which may contribute to the complex and severe phenotype. Mutation screening of the FHL1 gene should be considered for patients with uncharacterized myopathies and cardiomyopathies.