RESUMO
BACKGROUND: Recessive loss-of-function mutations in HINT1 are associated with predominantly motor axonal peripheral neuropathy with neuromyotonia. Twenty-four distinct pathogenic variants are reported all over the world, including four confirmed founder variations in Europe and Asia. The majority of patients carry the ancient Slavic founder variant c.110G>C (p.Arg37Pro) that shows a distribution gradient from east to west throughout Europe. METHODS: We report a case of HINT1 neuropathy in South America, identified by massive parallel sequencing of a neuropathy gene panel. To investigate the origin of the variant, we performed haplotyping analysis. RESULTS: A Brazilian adolescent presented with recessive axonal motor neuropathy with asymmetric onset and fasciculations. Neuromyotonia was found on needle electromyography. His parents were not consanguineous and had no European ancestry. The patient carried biallelic pathogenic p.Arg37Pro alterations in the first exon of HINT1. Both alleles were identical by descent and originated from the same ancestral founder allele as reported in Europe. CONCLUSION: Our findings expand the geographic distribution of HINT1 neuropathy to South America, where we describe a recognized founder variant in a Brazilian adolescent with no apparent European ancestry. We confirm the association of the hallmark sign of neuromyotonia with the disease.
Assuntos
Efeito Fundador , Síndrome de Isaacs/diagnóstico , Síndrome de Isaacs/genética , Mutação , Proteínas do Tecido Nervoso/genética , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/genética , Adolescente , Alelos , Substituição de Aminoácidos , Brasil , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , América do SulRESUMO
This study showed the prevalence of human papillomavirus (HPV) variants as well as nucleotide changes within L1 gene and LCR of the HPV16, HPV31, and HPV58 found in cervical lesions of women from North-East Brazil.
Assuntos
Genes Virais/genética , Variação Genética/genética , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Brasil/epidemiologia , Proteínas do Capsídeo/genética , Feminino , Humanos , Prevalência , Neoplasias do Colo do Útero/virologiaRESUMO
The influence of genic polymorphisms involved in metabolism of chemotherapeutic agents as the methotrexate (MTX) has been studied mainly in acute lymphoblastic leukemia (ALL) of childhood. Advances in treatment may be attributed to identification of prognostic factors added to chemotherapy protocol. The aim of this study was to analyze the association of the C677T, A1298C, and G80A polymorphisms on MTHFR gene and on the overall survival of pediatric patients (n = 126) with lymphoblastic leukemia treated with MTX according to the Brazilian protocol in 187 months. The C677T and G80A polymorphisms were genotyped by PCR-RFLP and A1298C polymorphism by allele-specific PCR. We observed that ALL patients presented rate (dead/alive) of 0.36 for the 677CC genotype, corresponding also to lower overall survival (P = 0.0013); on the other hand, the 677TT genotype showed a better survival (98%). Thus, we believe that patients with 80AA genotype presented a small reduction in MTX plasma level, suggesting that ALL children, carrying the 80AA genotype, showed a high toxicity to MTX (P < 0.0001).
Assuntos
Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 3/genética , Células Matadoras Naturais/patologia , Leucemia Mieloide Aguda/patologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Translocação Genética/genética , Adolescente , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Masculino , Fenótipo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , PrognósticoRESUMO
Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme in the metabolism of folate. The presence of polymorphisms that reduce the activity of MTHFR has been linked to the multifactor process of development of acute leukemia. A case control study was conducted on Brazilian children in different regions of the country with the aim of investigating the role of MTHFR C677T and A1298C polymorphisms as risk factors in the development of acute myeloid leukemia (AML). We used the polymerase chain reaction restriction fragment length polymorphism method to genotyping 182 AML and 315 healthy individuals. The genotype 677 CT was associated with decreased risk [odds ratio (OR), 0.37; confidence interval (CI) 95%, 0.14 - 0.92], whereas 1298 AC genotype was linked with an increased risk [OR, 2.90; CI 95%, 1.26 - 6.71] of developing AML in non-white children. Further epidemiological study is needed to unravel the complex multiple gene-environment interactions in the role of the AML leukemogenesis.