RESUMEN
Familial Mediterranean fever is inherited in an autosomal recessive manner. There are two phenotypes: types 1 and 2. Familial Mediterranean fever type 1 is characterized by recurrent short episodes of inflammation and serositis, including fever, peritonitis, synovitis, pleuritis, and, rarely, pericarditis. The symptoms and severity vary among affected individuals, sometimes even among members of the same family. Amyloidosis, which can lead to renal failure, is the most severe complication. Familial Mediterranean fever type 2 is characterized by amyloidosis as the first clinical manifestation of familial Mediterranean fever in an otherwise asymptomatic individual. Routine treatment of end-stage renal disease, including renal transplantation, is advised. Lifelong treatment with colchicine is required for homozygotes for the p.Met694Val mutation or compound heterozygotes for p.Met694Val and another disease-causing allele; this prevents the inflammatory attacks and the deposition of amyloid. Individuals who do not have the p.Met694Val mutation and who are only mildly affected should be either treated with colchicine or monitored every 6 months for the presence of proteinuria. Molecular genetic testing of the MEFV gene, the only gene currently known to be associated with familial Mediterranean fever, can be offered to family members, especially when the p.Met694Val allele is present, because renal amyloidosis can be prevented by colchicine.
Asunto(s)
Proteínas del Citoesqueleto/genética , Fiebre Mediterránea Familiar , Diagnóstico Diferencial , Fiebre Mediterránea Familiar/diagnóstico , Fiebre Mediterránea Familiar/epidemiología , Fiebre Mediterránea Familiar/genética , Fiebre Mediterránea Familiar/terapia , Estudios de Asociación Genética , Humanos , Mutación , PirinaRESUMEN
BACKGROUND: Long QT syndrome is an inherited cardiac disease, associated with malignant arrhythmias and sudden cardiac death. OBJECTIVES: To map and identify the gene responsible for LQTS in an Israeli family. METHODS: A large family was screened for LQTS after one of them was successfully resuscitated from ventricular fibrillation. The DNA was examined for suspicious loci by whole genome screening and the coding region of the LQT2 gene was sequenced. RESULTS: Nine family members, 6 males and 3 females, age (median and interquartile range) 26 years (13, 46), who were characterized by a unique T wave pattern were diagnosed as carrying the mutant gene. The LQTS-causing gene was mapped to chromosome 7 with the A614V mutation. All of the affected members in the family were correctly identified by electrocardiogram. Corrected QT duration was inversely associated with age in the affected family members and decreased with age. CONCLUSIONS: Careful inspection of the ECG can correctly identify LQTS in some families. Genetic analysis is needed to confirm the diagnosis and enable the correct therapy in this disease.
Asunto(s)
Cromosomas Humanos Par 7/genética , Canales de Potasio Éter-A-Go-Go/genética , Síndrome de QT Prolongado/genética , Mutación Missense , Adolescente , Adulto , Factores de Edad , Mapeo Cromosómico , Análisis Mutacional de ADN , Canal de Potasio ERG1 , Femenino , Humanos , Israel , Síndrome de QT Prolongado/diagnóstico , Síndrome de QT Prolongado/epidemiología , Masculino , Persona de Mediana Edad , Linaje , Adulto JovenRESUMEN
BACKGROUND: Fanconi anemia complementation group C and Bloom syndrome, rare autosomal recessive disorders marked by chromosome instability, are especially prevalent in the Ashkenazi* Jewish community. A single predominant mutation for each has been reported in Ahshkenazi Jews: c.711+4A-->T (IVS4 +4 A-->T) in FACC and BLM(Ash) in Bloom syndrome. Individuals affected by either of these syndromes are characterized by susceptibility for developing malignancies, and we questioned whether heterozygote carriers have a similarly increased risk. OBJECTIVES: To estimate the cancer rate among FACC and BLM(Ash) carriers and their families over three previous generations in unselected Ashkenazi Jewish individuals. METHODS: We studied 42 FACC carriers, 28 BLM(Ash) carriers and 43 controls. The control subjects were Ashkenazi Jews participating in our prenatal genetic screening program who tested negative for FACC and BLM(Ash). All subjects filled out a questionnaire regarding their own and a three-generation family history of cancer. The prevalence rates of cancer among relatives of FACC, BLM(Ash) and controls were computed and compared using the chi-square test. RESULTS: In 463 relatives of FACC carriers, 45 malignancies were reported (9.7%) including 10 breast (2.2%) and 13 colon cancers (2.8%). Among 326 relatives of BLM(Ash) carriers there were 30 malignancies (9.2%) including 7 breast (2.1%) and 4 colon cancers (1.2%). Controls consisted of 503 family members with 63 reported malignancies (12.5%) including 11 breast (2.2%) and 11 colon cancers (2.2%). CONCLUSIONS: We found no significantly increased prevalence of malignancies among carriers in at least three generations compared to the controls.
Asunto(s)
Síndrome de Bloom/etnología , Síndrome de Bloom/epidemiología , Neoplasias de la Mama/etnología , Neoplasias de la Mama/epidemiología , Neoplasias Colorrectales/etnología , Neoplasias Colorrectales/epidemiología , Anemia de Fanconi/etnología , Anemia de Fanconi/epidemiología , Heterocigoto , Judíos/genética , Mutación/genética , Adulto , Síndrome de Bloom/genética , Neoplasias de la Mama/genética , Estudios de Casos y Controles , Neoplasias Colorrectales/genética , Anemia de Fanconi/genética , Femenino , Humanos , Israel/epidemiología , Masculino , Prevalencia , Medición de RiesgoRESUMEN
Nonsyndromic mental retardation (NSMR) is the diagnosis of exclusion in mentally retarded individuals without additional abnormalities. We have recently identified a protein-truncating mutation, G408fsX437, in the gene CC2D1A on chromosome 19p13.12 in nine consanguineous Israeli Arab families with severe autosomal recessive NSMR, and have developed a comprehensive prevention program among the at-risk population in the village. The subjects tested were healthy women who were invited to undergo the genetic screening test as a part of their routine pregnancy monitoring. One hundred and seventeen subjects reported a family history positive for mental retardation. We tested 524 pregnant or preconceptional women and found 47 carriers (approximately 1/11), whose spouses were then recommended to undergo testing. We identified eight carrier couples, who were given genetic counseling and offered prenatal diagnosis. Of all the marriages, 28.6% were consanguineous; 16.5% of the total were between first cousins. The high prevalence of the mutation can be explained both by the founder effect owing to the generally high consanguinity rate among the inhabitants of the village, and also because two families with excessive numbers of mentally retarded offspring were unacceptable as marriage partners by the rest of the families. This is the first example of the establishment of a large-scale genetic screening program for autosomal recessive NSMR, which was made possible owing to the high frequency of the specific causative mutation in this isolated population.
Asunto(s)
Proteínas de Unión al ADN/genética , Genes Recesivos , Pruebas Genéticas , Discapacidad Intelectual/diagnóstico , Diagnóstico Prenatal , Femenino , Asesoramiento Genético , Homocigoto , Humanos , Discapacidad Intelectual/genética , Israel , Población/genética , EmbarazoRESUMEN
Consanguineous marriages are associated with many problems, although the prevailing opinion is that the advantages outweigh the disadvantages. This explains why the custom is still extremely prevalent, particularly in Arab countries, India and small isolated communities. Among Israeli Arabs there has been a reduction in the rate of such marriages, although it is still sufficiently high to cause medical problems. Among Israeli Jews, the rate has always been much lower. Future goals are to expand the educational programs aimed at the Israeli Arab community and to promote the uptake of genetic counseling and prenatal testing where available in order to reduce the health problems even further. Ongoing research in order to identify specific genes will enable more conditions to be detectable early in pregnancy. We expect that the willingness of families to agree to termination of affected pregnancies will reduce the number of babies born with these conditions.
Asunto(s)
Árabes/genética , Consanguinidad , Enfermedades Genéticas Congénitas/genética , Judíos/genética , Adulto , Árabes/etnología , Preescolar , Femenino , Asesoramiento Genético , Enfermedades Genéticas Congénitas/etnología , Enfermedades Genéticas Congénitas/prevención & control , Humanos , Recién Nacido , Israel , Judíos/etnología , Masculino , Diagnóstico PrenatalRESUMEN
PURPOSE: To evaluate the level of knowledge among adolescents about the issues associated with consanguinity, because consanguineous marriages are widely practiced among Arabs, and are associated with an increased incidence of congenital malformations. METHODS: We carried out a national survey among 2933 students aged 15-16 years within the Israeli Arab community. Variables considered were gender, religion, location of residence, parents' level of education, number of siblings, whether their parents' marriage was consanguineous, whether any family members had congenital malformations, and the respondents' religious beliefs and traditions. Association among those variables and the level of knowledge that were statistically significant by univariate analysis were also assessed in a multivariate model. RESULTS: One-quarter of the students (24.5%) demonstrated a high level of knowledge, whereas 29.7% had a moderate level and 45.8% a low level. Overall, 81.5% knew that consanguinity was associated with a high incidence of congenital malformations, although only half of these (50.0%) knew what congenital malformations were and which were associated with consanguinity. The variables significantly associated with a low level of knowledge were gender, level of parents' education, consanguinity between the students' parents, and extreme religious attitudes. CONCLUSIONS: Efforts to increase the knowledge of Israeli Arab adolescents about consanguinity should therefore be especially directed toward males with parents who have a lower level of education, with parents who are consanguineous, and who have extreme religious attitudes.
Asunto(s)
Árabes , Concienciación , Anomalías Congénitas/etiología , Consanguinidad , Adolescente , Escolaridad , Femenino , Humanos , Incidencia , Israel/epidemiología , Masculino , Encuestas y CuestionariosRESUMEN
BACKGROUND: The infant mortality rate is a health status indicator. OBJECTIVES: To analyze the differences in infant mortality rates between Jews and Arabs in Israel between 1975 and 2000. METHODS: Data were used from the Central Bureau of Statistics and the Department of Mother, Child and Adolescent Health in the Ministry of Health. RESULTS: The IMR in 2000 was 8.6 per 1,000 live births in the Israeli Arab population as compared to 4.0 in the Jewish population. Between 1970 and 2000 the IMR decreased by 78% among Moslems, 82% among Druze, and 88% among Christians, as compared to 79% in the Jewish population. In 2000, in the Arab population, 40% of all infant deaths were caused by congenital malformations and 29% by prematurity, compared to 23% and 53%, respectively, in the Jewish population. Between 1970 and 2000 the rate of congenital malformations declined in both the Arab and Jewish populations. In the 1970s the rate was 1.4 times higher in the Arab community than in the Jewish community, and in 2000 it was 3.7 times higher. CONCLUSION: As in the Jewish population, the IMR in the Arab community has decreased over the years, although it is still much higher than that in the Jewish community. Much remains to be done to reduce the incidence of congenital malformations among Arabs, since this is the main cause of the high IMR in this population.
Asunto(s)
Mortalidad Infantil/tendencias , Árabes/etnología , Árabes/estadística & datos numéricos , Anomalías Congénitas/epidemiología , Indicadores de Salud , Humanos , Recién Nacido , Recien Nacido Prematuro , Israel/epidemiología , Judíos/etnología , Judíos/estadística & datos numéricosRESUMEN
Myotonic dystrophy is the commonest autosomal dominant type of muscular dystrophy in adults. It is one of the trinucleotide repeat expansion disorders, and its severity correlates with the number of CTG repeats in the myotonic dystrophy gene. It has been suggested that myotonic dystrophy exhibits the phenomenon of preferential transmission of the larger mutated alleles that has been described in other trinucleotide repeat disorders. Several authors have reported that the frequency of transmission of the mutated alleles is higher than 50%--a finding that, if true, does not comply with the Mendelian laws of segregation. However, these studies were based on data from the analysis of pedigrees with ascertainment bias. In our study, we determined the frequency of transmission of mutated alleles using data from prenatal molecular studies, which are not subject to ascertainment bias. This is the first study to examine the segregation of the mutated alleles in myotonic dystrophy in pregnancy. Eighty-three fetuses were examined, 30 of 62 mothers (48.38%) and 8 of 21 fathers (38.09%) transmitted the mutated allele, giving an overall transmission rate of 45.78%. We found no evidence of statistically significant deviation of the frequency of transmission of the mutated alleles from the 50% expected in autosomal dominant disorders. This study, unlike previous ones, excludes preferential transmission in myotonic dystrophy, a finding that may be attributable to the lack of correction for ascertainment bias in previous studies and to the use of prenatal data in this study.