Molecular Genetic Anatomy and Risk Profile of Hirschsprung’s Disease (Record no. 12951)
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| 000 -CABECERA | |
|---|---|
| campo de control de longitud fija | 03467nab a2200277 4500 |
| 003 - NÚMERO DE CONTROL | |
| campo de control | CO-MdCUR |
| 005 - FECHA Y HORA DE ACTUALIZACIÓN | |
| 005 | 20190726110603.0 |
| 007 - CAMPO FIJO DE DESCRIPCIÓN FÍSICA--INFORMACIÓN GENERAL | |
| campo de control de longitud fija | ta |
| 008 - LONGITUD FIJA | |
| campo de control de longitud fija | 170814s2019 xxu||||| |||| 00| 0 eng d |
| 040 ## - FUENTE DE CATALOGACIÓN | |
| Centro/agencia transcriptor | Remington |
| Centro catalogador/agencia de origen | CO-MdCUR |
| Normas de descripción | rda |
| 041 ## - IDIOMA | |
| Código de idioma | Inglés |
| 082 ## - CLASIFICACIÓN DECIMAL DEWEY | |
| edición | 21 |
| 773 0# - ENLACE AL DOCUMENTO FUENTE | |
| Número bibliográfico anfitrión | 11137 |
| Número de ítem anfitrión | 23480 |
| Encabezamiento principal | Massachusetts Medical Society |
| Lugar, editor y fecha de publicación | Boston, Massachusetts Medical Society. |
| Otro identificador del documento | 19653 |
| Título | The New England journal of medicine. |
| Número de control del registro | 11137412 |
| Número Internacional Normalizado para Publicaciones Seriadas | 0028-4793 |
| 100 1# - AUTOR PERSONAL | |
| 9 (RLIN) | 39379 |
| nombre | Tilghman, Joseph M. |
| 245 1# - TÍTULO PROPIAMENTE DICHO | |
| título | Molecular Genetic Anatomy and Risk Profile of Hirschsprung’s Disease |
| 264 ## - PIE DE IMPRENTA | |
| lugar (ciudad) | Boston : |
| editorial | Massachusetts Medical Society , |
| fecha | 2019 |
| 300 ## - DESCRIPCIÓN FÍSICA | |
| Extensión | páginas 1421 - 1432 |
| 520 3# - RESUMEN | |
| Resumen | BACKGROUND<br/>Hirschsprung’s disease, or congenital aganglionosis, is a developmental disorder of the enteric nervous system and is the most common cause of intestinal obstruction in neonates and infants. The disease has more than 80% heritability, including significant associations with rare and common sequence variants in genes related to the enteric nervous system, as well as with monogenic and chromosomal syndromes.<br/><br/>METHODS<br/>We genotyped and exome-sequenced samples from 190 patients with Hirschsprung’s disease to quantify the genetic burden in patients with this condition. DNA sequence variants, large copy-number variants, and karyotype variants in probands were considered to be pathogenic when they were significantly associated with Hirschsprung’s disease or another neurodevelopmental disorder. Novel genes were confirmed by functional studies in the mouse and human embryonic gut and in zebrafish embryos.<br/><br/>RESULTS<br/>The presence of five or more variants in four noncoding elements defined a widespread risk of Hirschsprung’s disease (48.4% of patients and 17.1% of controls; odds ratio, 4.54; 95% confidence interval [CI], 3.19 to 6.46). Rare coding variants in 24 genes that play roles in enteric neural-crest cell fate, 7 of which were novel, were also common (34.7% of patients and 5.0% of controls) and conferred a much greater risk than noncoding variants (odds ratio, 10.02; 95% CI, 6.45 to 15.58). Large copy-number variants, which were present in fewer patients (11.4%, as compared with 0.2% of controls), conferred the highest risk (odds ratio, 63.07; 95% CI, 36.75 to 108.25). At least one identifiable genetic risk factor was found in 72.1% of the patients, and at least 48.4% of patients had a structural or regulatory deficiency in the gene encoding receptor tyrosine kinase (RET). For individual patients, the estimated risk of Hirschsprung’s disease ranged from 5.33 cases per 100,000 live births (approximately 1 per 18,800) to 8.38 per 1000 live births (approximately 1 per 120).<br/><br/>CONCLUSIONS<br/>Among the patients in our study, Hirschsprung’s disease arose from common noncoding variants, rare coding variants, and copy-number variants affecting genes involved in enteric neural-crest cell fate that exacerbate the widespread genetic susceptibility associated with RET. For individual patients, the genotype-specific odds ratios varied by a factor of approximately 67, which provides a basis for risk stratification and genetic counseling. (Funded by the National Institutes of Health.) |
| 650 #0 - MATERIA GENERAL | |
| 9 (RLIN) | 29547 |
| Término de materia o nombre geográfico como elemento inicial | Enfermedad de Hirschsprung |
| 700 1# - COAUTOR PERSONAL | |
| 9 (RLIN) | 39380 |
| Nombre de persona | Ling, Albee Y. |
| 700 1# - COAUTOR PERSONAL | |
| 9 (RLIN) | 39381 |
| Nombre de persona | Turner, Tychele N. |
| 942 ## - PUNTO DE ACCESO ADICIONAL KOHA | |
| Fuente del sistema de clasificación o colocación | Dewey Decimal Classification |
| Tipo de ítem Koha | Hemeroteca |
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