RESUMO
Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder characterized by multiple motor tics and at least one vocal or phonic tic, and often one or more comorbid psychiatric disorders. Premonitory sensory urges before tic execution and desire for "just-right" perception are central features. The pathophysiology involves cortico-striato-thalamo-cortical circuits and possibly dopaminergic system. TS is considered a genetic disorder but the genetics is complex and likely involves rare mutations, common variants, and environmental and epigenetic factors. Treatment is multimodal and includes education and reassurance, behavioral interventions, pharmacologic, and rarely, surgical interventions.
Assuntos
Síndrome de Tourette/diagnóstico , Síndrome de Tourette/terapia , Idade de Início , Criança , Comorbidade , Humanos , Anamnese , Testes Neuropsicológicos , Exame Físico , Fatores de Risco , Síndrome de Tourette/genética , Síndrome de Tourette/fisiopatologiaRESUMO
There is significant male excess in autism. In this study, we investigated a possible Y chromosome effect by haplotype analysis. We investigated 12 single-nucleotide polymorphisms in Y-linked neuroligin 4, transducin beta-like 1, and eukaryotic translation initiation factor 1a genes in 146 autistic participants and 102 control participants of European American origin. The set of 12 single-nucleotide polymorphisms defined 9 Y chromosome haplotypes in autistic and control participants. Although the 2 most frequent haplotypes were equally distributed in the autistic and control participants, some haplotypes were overrepresented or underrepresented in autistic participants. The distribution of haplotypes between the autistic and control groups, as determined by Monte Carlo tests with Clump software, was significantly different (P = .0001 with 100,000 simulations). Our results are suggestive of a Y chromosome effect in autism.
Assuntos
Transtorno Autístico/genética , Proteínas de Transporte/genética , Fator de Iniciação 1 em Eucariotos/genética , Haplótipos , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Transducina/genética , Estudos de Casos e Controles , Moléculas de Adesão Celular Neuronais , Cromossomos Humanos Y , Simulação por Computador , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Método de Monte Carlo , Razão de Chances , Análise de Sequência de DNA , Estados Unidos , População Branca/genéticaRESUMO
Myotonic dystrophy is considered a true dominant condition with no difference in the phenotype between heterozygous and homozygous cases. The homozygous state is very rare and only a few patients have been reported in the literature. We report a 2.5-year-old boy from a nonconsanguineous marriage, with a unique combination of clinical and radiological findings: hypotonia, motor and language developmental delay, ventriculomegaly, subcortical white matter lesions, and craniosynostosis. Mutation analysis revealed 2 copies of expansion mutation of 1260 and 60 cytosine-thymine-guanine repeats in the myotonic dystrophy protein kinase gene. Both the mildly symptomatic (434 repeats) mother and the asymptomatic (37 repeats) father are heterozygous. Craniosynostosis has not been reported previously in myotonic dystrophy. This homozygous case expands the clinical spectrum of myotonic dystrophy type 1 and provides support to the hypothesis that myotonic dystrophy type 1 pathophysiology could be, in part, due to the loss of normal function of the wild-type protein.
Assuntos
Craniossinostoses/genética , Análise Mutacional de DNA , Homozigoto , Distrofia Miotônica/genética , Proteínas Serina-Treonina Quinases/genética , Alelos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Pré-Escolar , Suturas Cranianas/diagnóstico por imagem , Craniossinostoses/diagnóstico , Citosina/metabolismo , Expansão das Repetições de DNA/genética , Guanina/metabolismo , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Transtornos do Desenvolvimento da Linguagem/genética , Masculino , Distrofia Miotônica/diagnóstico , Miotonina Proteína Quinase , Exame Neurológico , Fenótipo , Radiografia , Crânio/diagnóstico por imagem , Timina/metabolismoRESUMO
Genome scans indicate a linkage of autism to the chromosome 7q21-q36 region. Recent studies suggest that the Reelin gene may be one of the loci contributing to the positive linkage between chromosome 7q and autism. However, these studies were relatively small scale, using a few markers in the gene. We investigated 34 single nucleotide polymorphisms (SNPs) in the Reelin gene with an average spacing between the SNPs of 15 kb for evidence of association with autism. There were significant differences in the transmission of the alleles of exon 22 and intron 59 SNP to autistic subjects. Our findings support a role for the Reelin gene in the susceptibility to autism.
Assuntos
Transtorno Autístico/genética , Moléculas de Adesão Celular Neuronais/genética , Cromossomos Humanos Par 7/genética , Proteínas da Matriz Extracelular/genética , Ligação Genética , Predisposição Genética para Doença , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único/genética , Serina Endopeptidases/genética , Alelos , Estudos de Casos e Controles , Éxons/genética , Feminino , Humanos , Íntrons/genética , Masculino , Proteína ReelinaAssuntos
Transtorno Autístico/genética , Variação Genética/genética , Isoenzimas/fisiologia , Fosfatidilinositol 3-Quinases/fisiologia , Fosfatidilinositóis/fisiologia , Monoéster Fosfórico Hidrolases/fisiologia , Proteínas Repressoras/fisiologia , Transdução de Sinais/genética , Criança , Classe Ib de Fosfatidilinositol 3-Quinase , Feminino , Haplótipos/genética , Humanos , Isoenzimas/genética , Desequilíbrio de Ligação/genética , Masculino , Computação Matemática , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositóis/genética , Monoéster Fosfórico Hidrolases/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas Repressoras/genética , Proteína 2 do Complexo Esclerose Tuberosa , Proteínas Supressoras de TumorRESUMO
We report a patient with a unique combination of clinical findings: XY sex reversal, spastic paraplegia, mental retardation, dysmorphism, and infantile-onset olivopontocerebellar hypoplasia. The phenotype of our patient did not coincide with any of the described forms of XY reversal syndromes, hereditary or sporadic spastic paraplegias, or congenital or infantile-onset cerebellar or olivopontocerebellar atrophies or hypoplasias. The disorder of this patient likely represents a genetic condition with pleiotropic effects on brain development and sex determination and adds further evidence for the heterogeneity of spastic paraplegia/infantile olivopontocerebellar hypoplasia syndromes and sex reversal syndromes.
Assuntos
Encéfalo/anormalidades , Transtornos do Desenvolvimento Sexual , Disgenesia Gonadal 46 XY/genética , Doenças do Sistema Nervoso/genética , Paraplegia/genética , Criança , Feminino , Disgenesia Gonadal 46 XY/diagnóstico , Humanos , Doenças do Sistema Nervoso/diagnóstico , Paraplegia/diagnósticoRESUMO
Circulating hematopoietic stem cells were collected by three consecutive leukaphereses during post-chemotherapy expansion of the stem cell pool in a 3-year-old boy with advanced and therapy-resistant neuroblastoma. The cells were fractionated by discontinuous Percoll gradient centrifugation, frozen in a programmed freezer and then stored in liquid nitrogen. Following high-dose chemotherapy, the cells were thawed rapidly and re-infused into the patient. Early evidence of marrow recovery was first noted at day 13 and the times required to achieve a granulocyte count of greater than 0.5 x 10(9)/L and a platelet count of greater than 50 x 10(9)/L were 21 days and 30 days, respectively. This new marrow-rescue operation may have potential in cancer therapy as an alternative to bone marrow transplantation and further clinical investigation is warranted.
