RESUMEN
INTRODUCTION: Genetic tests are developing quickly. Therefore, genetic screening tests which were carried out before the first pregnancy are not always sufficient for the subsequent pregnancies. Familial dysautonomia (FD) is a disabling autosomal recessive disorder affecting Ashkenazi Jews in which the carrier frequency varies from 1:17 to 1:32. In 2001, the FD gene was discovered and the genetic tests were made available in most Israeli hospitals or institutes. In 2008, the FD genetic test was included in the "health basket" by the Israeli Ministry of Health. AIMS: Investigating the reasons for new FD patients born after 2001 as a model for other genetic diseases. METHODS: A retrospective study was performed from medical chart data. RESULTS: Since 2001, forty FD patients were born to Israeli parents. Eleven patients were born to mothers who had undergone genetic tests before 2001, however, they were not informed that new genes had been discovered. This has led to a number of law suits. Furthermore, the FD test was not offered to another woman who had some of the genetic tests performed after 2001. Religious parents of 9 FD patients had married long before the FD genetic test became avaiLable. Four children were born to families who were unaware that there was an FD patient in their extended family. DISCUSSION AND SUMMARY: The burden on the patients, families and the National Health Service for treating FD and other genetic diseases is enormous. Updating new genetic information might prevent new cases. CONCLUSIONS: Before each new pregnancy, it is necessary to update the population about new genetic tests.
Asunto(s)
Disautonomía Familiar , Asesoramiento Genético/tendencias , Pruebas Genéticas/tendencias , Complicaciones del Embarazo , Costo de Enfermedad , Disautonomía Familiar/diagnóstico , Disautonomía Familiar/etnología , Disautonomía Familiar/genética , Femenino , Predicción , Humanos , Israel/epidemiología , Judíos/genética , Linaje , Embarazo , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/etnología , Complicaciones del Embarazo/genética , Diagnóstico Prenatal/métodosRESUMEN
Familial Dysautonomia is an autosomal recessive disease with a remarkably high carrier frequency in the Ashkenazi Jewish population. It has recently been estimated that as many as 1 in 27 Ashkenazi Jews is a carrier of FD. The FD gene has been identified as IKBKAP, and two disease-causing mutations have been identified. The most common mutation, which is present on 99.5% of all FD chromosomes, is an intronic splice site mutation that results in tissue-specific skipping of exon 20. The second mutation, R696P, is a missense mutation that has been identified in 4 unrelated patients heterozygous for the major splice mutation. Interestingly, despite the fact that FD is a recessive disease, normal mRNA and protein are expressed in patient cells. To date, the diagnosis of FD has been limited to individuals of Ashkenazi Jewish descent and identification of the gene has led to widespread diagnostic and carrier testing in this population. In this report, we describe the first non-Jewish IKBKAP mutation, a proline to leucine missense mutation in exon 26, P914L. This mutation is of particular significance because it was identified in a patient who lacks one of the cardinal diagnostic criteria for the disease-pure Ashkenazi Jewish ancestry. In light of this fact, the diagnostic criteria for FD must be expanded. Furthermore, in order to ensure carrier identification in all ethnicities, this mutation must now be considered when screening for FD.
Asunto(s)
Disautonomía Familiar/etnología , Disautonomía Familiar/genética , Mutación Missense/genética , Preescolar , Análisis Mutacional de ADN , Humanos , Judíos/genética , Mapeo RestrictivoAsunto(s)
Análisis Mutacional de ADN , Disautonomía Familiar/genética , Pruebas Genéticas , Judíos/genética , Chaperonas Moleculares , Mucolipidosis/genética , Síndrome de Tourette/genética , Alelos , Sustitución de Aminoácidos , Proteínas Portadoras/genética , Disautonomía Familiar/etnología , Frecuencia de los Genes , Genes Dominantes , Genes Recesivos , Enfermedades Genéticas Congénitas/etnología , Enfermedades Genéticas Congénitas/genética , Heterocigoto , Humanos , Incidencia , Judíos/clasificación , Proteínas de la Membrana/genética , Mucolipidosis/epidemiología , Mutación , Mutación Missense , Canales Catiónicos TRPM , Síndrome de Tourette/etnología , Factores de Elongación Transcripcional , Canales de Potencial de Receptor TransitorioRESUMEN
Familial dysautonomia (DYS), the Riley-Day syndrome, is an autosomal recessive disorder characterized by developmental loss of neurons from the sensory and autonomic nervous system. It is limited to the Ashkenazi Jewish population, where the carrier frequency is 1 in 30. We have mapped the DYS gene to chromosome 9q31-q33 by linkage with ten DNA markers in 26 families. The maximum lod score of 21.1 with no recombinants was achieved with D9S58. This marker also showed strong linkage disequilibrium with DYS, with one allele present on 73% of affected chromosomes compared to 5.4% of controls (chi 2 = 3142, 15 d.f. p < 0.0001). D9S53 and D9S105 represent the closest flanking markers for the disease gene. This localization will permit prenatal diagnosis of DYS in affected families and aid the isolation of the disease gene.