Assuntos
Anormalidades Múltiplas/diagnóstico por imagem , Encéfalo/anormalidades , Hibridização Genômica Comparativa , Sindactilia/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Adulto , Ecoencefalografia , Feminino , Humanos , Fatores de Transcrição Kruppel-Like/genética , Proteínas do Tecido Nervoso/genética , Síndrome , Proteína Gli3 com Dedos de ZincoRESUMO
BACKGROUND: The use of microarray-based comparative genomic hybridization has allowed the genetic diagnosis of some conditions before their full clinical presentation. This "genotype-first" diagnosis has the most clinical implications for genomic alterations that confer an elevated risk of cancer. In these cases, diagnosis before the manifestation of the patient's full phenotype dramatically impacts genetic counseling, clinical management, and eventual prognosis and survivability. METHODS: Using microarray-based comparative genomic hybridization, we tested 18,437 individuals with indications such as developmental disabilities and congenital anomalies. RESULTS: We identified 34 (0.18%) individuals with DNA copy number gains or losses that encompassed gene regions associated with recognized genetic conditions with an increased risk for cancer. Three of the 34 individuals (8.8%) had a previously abnormal cytogenetic study which microarray-based comparative genomic hybridization confirmed and/or further characterized. Seven of the 34 individuals (20.6%) either had the correct disease specified in the clinical indication for study or had clinical features highly indicative of that syndrome. The remaining 24 patients (70.6%) had indications for study that were not specific to the diagnosed syndrome, such as "developmental delay" or "dysmorphic features." CONCLUSIONS: The ability of microarray-based comparative genomic hybridization to rapidly and objectively interrogate the genome for chromosomal imbalances has led to the opportunity to optimize medical management and outcome. This has an even more profound impact and clinical utility in conditions associated with cancer predisposition syndromes.
Assuntos
Hibridização Genômica Comparativa/estatística & dados numéricos , Anormalidades Congênitas/genética , Deficiências do Desenvolvimento/genética , Duplicação Gênica , Predisposição Genética para Doença/genética , Neoplasias/genética , Deleção de Sequência/genética , Pré-Escolar , Hibridização Genômica Comparativa/métodos , Humanos , Cariotipagem , Análise em Microsséries/métodosRESUMO
In the past century, various methods to visualize human chromosomes were discovered. Chromosome analyses provide an overall view of the human genome that cannot be achieved with any other approach. The methods to visualize chromosomes include various techniques to produce bands along chromosomes, specialized procedures for specific disorders, and fluorescent-labeled DNA for targeted loci. Cytogenetic methods guide the study of the relationship between chromosome structure and gene function. They also aid in mapping locations of genes and identifying chromosome anomalies associated with medical disorders. The clinical diagnosis, prognosis, and response to treatment can be established for many malignant diseases. Cytogenetic methods provide an important diagnostic tool for clinical practice.
