RESUMO
Background and Objectives: Congenital thyroid dyshormonogenesis is caused by alterations in the synthesis of thyroid hormones in a newborn. Additionally, 10 to 20% of these cases are hereditary, caused by defects in proteins involved in hormonal synthesis. One of the most common causes is mutations in the thyroid peroxidase (TPO) enzyme gene, an autosomal recessive disease. We aimed to detect mutations of the TPO gene in 12 Chilean patients with congenital hypothyroidism due to dyshormonogenesis (CHD) and to characterize these patients clinically and molecularly. Materials and Methods: Twelve patients under 20 years of age with CHD, controlled at San Juan de Dios Hospital in Santiago, Chile, were selected according to the inclusion criteria: elevated neonatal TSH, persistent hypothyroidism, and thyroid normotopic by imaging study. Those with deafness, Down syndrome, and central or transient congenital hypothyroidism were excluded. Blood samples were taken for DNA extraction, and the 17 exons and exon-intron junctions of the TPO gene were amplified by PCR. The PCR products were sequenced by Sanger. Results: Two possibly pathogenic mutations of the TPO gene were detected: c.2242G>A (p.Val748Met) and c.1103C>T (p.Pro368Leu). These mutations were detected in 2 of 12 patients (16.6%): 1 was compound heterozygous c.1103C>T/c.2242G>A, and the other was heterozygous for c.2242G>A. In the diagnostic confirmation test, both patients presented diffuse hyper-uptake goiter on thyroid scintigraphy and high TSH in venous blood (>190 uIU/mL). Conclusions: The frequency of patients with possibly pathogenic mutations in TPO with CHD was 16.6%. Its study would allow for genetic counseling to be offered to the families of affected patients.
Assuntos
Hipotireoidismo Congênito , Iodeto Peroxidase , Proteínas de Ligação ao Ferro , Mutação , Humanos , Hipotireoidismo Congênito/genética , Hipotireoidismo Congênito/sangue , Chile , Iodeto Peroxidase/genética , Feminino , Masculino , Proteínas de Ligação ao Ferro/genética , Autoantígenos/genética , Lactente , Criança , Adolescente , Pré-Escolar , Recém-Nascido , Disgenesia da Tireoide/genética , Disgenesia da Tireoide/complicações , Disgenesia da Tireoide/sangueAssuntos
Qualidade de Vida , Traqueostomia , Traduções , Humanos , Inquéritos e Questionários , Idioma , EspanhaRESUMO
Background: Two new SNPs have been recently associated to Alzheimer's disease in African American populations: FCGRIIB rs1050501 C/T, and PILRA rs1859788 A/G. The risk of Alzheimer's disease in FCGRIIB C and PILRA A allele carriers is three times higher than in non-carriers. However, the association between these and other single nucleotide polymorphisms (SNPs) has not been assessed. Methods: Linkage disequilibrium analysis, with r= 0.8 as a threshold value, was used to impute new candidate SNPs, on genomic data from both genes in 26 populations worldwide (n= 2504) from the 1000Genomes database. Results: Four SNPs (rs13376485, rs3767640, rs3767639 and rs3767641) were linked to rs1050501 and one (rs2405442) to rs1859788 in the whole sample. Conclusions: Five novel SNPs could be associated with Alzheimer's disease susceptibility and play a causal role, even if none of them are exon variants since their potential roles in the regulation of gene expression.
Antecedentes: Recientemente se han asociado dos nuevos polimorfismos de un solo nucleótido (SNP) a la enfermedad de Alzheimer en poblaciones afroamericanas: FCGRIIB rs1050501 C/T, y PILRA rs1859788 A/G. El riesgo de enfermedad de Alzheimer en los portadores de los alelos FCGRIIB C y PILRA A es tres veces mayor que en los no portadores. Sin embargo, no se ha evaluado la asociación entre estos y otros SNP. Métodos: Se utilizó el análisis de desequilibrio de ligamiento, con r2= 0,8 como valor umbral, para imputar nuevos SNPs candidatos, sobre datos genómicos de ambos genes en 26 poblaciones de todo el mundo (n= 2504) de la base de datos 1000Genomes. Resultados: Cuatro SNPs (rs13376485, rs3767640, rs3767639 y rs3767641) se vincularon al rs1050501 y uno (rs2405442) al rs1859788 en toda la muestra. Conclusiones: Cinco nuevos SNP podrían estar asociados con la susceptibilidad a la enfermedad de Alzheimer y desempeñar un papel causal, aunque ninguno de ellos sea una variante de exón, dado su papel potencial en la regulación de la expresión génica.
Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/genética , Predisposição Genética para Doença , Desequilíbrio de Ligação , Glicoproteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Receptores Imunológicos/genéticaRESUMO
BACKGROUND: Two new SNPs have been recently associated to Alzheimer's disease in African American populations: FCGRIIB rs1050501 C/T, and PILRA rs1859788 A/G. The risk of Alzheimer's disease in FCGRIIB C and PILRA A allele carriers is three times higher than in non-carriers. However, the association between these and other single nucleotide polymorphisms (SNPs) has not been assessed. METHODS: Linkage disequilibrium analysis, with r= 0.8 as a threshold value, was used to impute new candidate SNPs, on genomic data from both genes in 26 populations worldwide (n= 2504) from the 1000Genomes database. RESULTS: Four SNPs (rs13376485, rs3767640, rs3767639 and rs3767641) were linked to rs1050501 and one (rs2405442) to rs1859788 in the whole sample. CONCLUSIONS: Five novel SNPs could be associated with Alzheimer's disease susceptibility and play a causal role, even if none of them are exon variants since their potential roles in the regulation of gene expression.
ANTECEDENTES: Recientemente se han asociado dos nuevos polimorfismos de un solo nucleótido (SNP) a la enfermedad de Alzheimer en poblaciones afroamericanas: FCGRIIB rs1050501 C/T, y PILRA rs1859788 A/G. El riesgo de enfermedad de Alzheimer en los portadores de los alelos FCGRIIB C y PILRA A es tres veces mayor que en los no portadores. Sin embargo, no se ha evaluado la asociación entre estos y otros SNP. MÉTODOS: Se utilizó el análisis de desequilibrio de ligamiento, con r2= 0,8 como valor umbral, para imputar nuevos SNPs candidatos, sobre datos genómicos de ambos genes en 26 poblaciones de todo el mundo (n= 2504) de la base de datos 1000Genomes. RESULTADOS: Cuatro SNPs (rs13376485, rs3767640, rs3767639 y rs3767641) se vincularon al rs1050501 y uno (rs2405442) al rs1859788 en toda la muestra. CONCLUSIONES: Cinco nuevos SNP podrían estar asociados con la susceptibilidad a la enfermedad de Alzheimer y desempeñar un papel causal, aunque ninguno de ellos sea una variante de exón, dado su papel potencial en la regulación de la expresión génica.
Assuntos
Humanos , Doença de Alzheimer/genética , Glicoproteínas de Membrana/genética , Receptores Imunológicos/genética , Desequilíbrio de Ligação , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Fundamento: el apoyo de familiares y del equipo de salud a los padres cuidadores de sus hijos diabéticos es fundamental para el afrontamiento a los cambios que provoca esta enfermedad en la dinámica familiar. Objetivo: describir la percepción de los padres cuidadores sobre el apoyo familiar y de los Sistemas de Salud en el comienzo de sus hijos con diabetes mellitus tipo 1. Métodos: estudio cualitativo descriptivo realizado mediante entrevista semiestructurada a cuatro padres cuidadores de niños con diagnóstico de diabetes tipo 1. El consentimiento informado fue realizado vía Google Forms y la entrevista fue vía plataforma ZOOM. Las entrevistas tuvieron una duración de 30 minutos. El análisis de las entrevistas se realizó utilizando el programa ATLAS.ti versión 22. Resultados: el comienzo de la enfermedad de los niños fue recibido por los padres con mucha confusión y falta de conocimiento. En cuanto a las redes de apoyo, los padres declararon la soledad como vivencia en el cuidado de los niños y, en relación a los equipos de salud, relataron que está enfocada en los cuidados básicos que tenían que cumplir, como la alimentación y el control glucémico, con ausencia de preocupación por el apoyo emocional. Conclusiones: las necesidades de apoyo desde los equipos de salud, a los padres cuidadores, más allá del control de la enfermedad, es una necesidad explícita desde la evidencia, que aún no ha sido considerada por los Sistemas de Salud. El apoyo debe trascender la familia, con una actuación importante de los profesionales de la salud y todo el contexto en que están insertos los niños, para contribuir a un manejo adecuado de la enfermedad.
Foundation: the support of family members and the health team for parents caring for their diabetic children is essential for facing with the changes that this disease causes in family dynamics. Objective: to describe the perception of parent caregivers about family support and Health Systems at the beginning of their children with type 1 diabetes mellitus. Methods: qualitative descriptive study carried out through semi-structured interviews with four parent caregivers of children with a diagnosis of type 1 diabetes. Informed consent was carried out via Google forms and the interview was via the ZOOM platform. The interviews lasted 30 minutes. The analysis of the interviews was carried out using the ATLAS.ti version 22 program. Results: the beginning of the children's illness was received by parents with much confusion and lack of knowledge. Regarding the support networks, the parents declared loneliness in the experience of caring for the children and, in relation to the health teams, they reported that it is focused on the basic care that they had to fulfill, such as food and hygiene, glycemic control, with absence of concern for emotional support. Conclusions: the support needs from health teams to parent caregivers, beyond disease control, is an explicit need from the evidence, which has not yet been considered by Health Systems. Support must go beyond the family, with important action by health professionals and the entire context in which children are inserted, to contribute to adequate management of the disease.