Jewish and Middle Eastern non-Jewish populations share a common pool of Y-chromosome biallelic haplotypes. (41/808)

Haplotypes constructed from Y-chromosome markers were used to trace the paternal origins of the Jewish Diaspora. A set of 18 biallelic polymorphisms was genotyped in 1,371 males from 29 populations, including 7 Jewish (Ashkenazi, Roman, North African, Kurdish, Near Eastern, Yemenite, and Ethiopian) and 16 non-Jewish groups from similar geographic locations. The Jewish populations were characterized by a diverse set of 13 haplotypes that were also present in non-Jewish populations from Africa, Asia, and Europe. A series of analyses was performed to address whether modern Jewish Y-chromosome diversity derives mainly from a common Middle Eastern source population or from admixture with neighboring non-Jewish populations during and after the Diaspora. Despite their long-term residence in different countries and isolation from one another, most Jewish populations were not significantly different from one another at the genetic level. Admixture estimates suggested low levels of European Y-chromosome gene flow into Ashkenazi and Roman Jewish communities. A multidimensional scaling plot placed six of the seven Jewish populations in a relatively tight cluster that was interspersed with Middle Eastern non-Jewish populations, including Palestinians and Syrians. Pairwise differentiation tests further indicated that these Jewish and Middle Eastern non-Jewish populations were not statistically different. The results support the hypothesis that the paternal gene pools of Jewish communities from Europe, North Africa, and the Middle East descended from a common Middle Eastern ancestral population, and suggest that most Jewish communities have remained relatively isolated from neighboring non-Jewish communities during and after the Diaspora.  (+info)

The impact of new immigrants from the former Soviet Union on the severity of coronary angiographic findings in a public hospital in Israel. (42/808)

BACKGROUND: The arrival of 610,000 new immigrants to Israel from the former Soviet republics accounted for 58% of the population growth in the early 1990's. OBJECTIVE: To compare the coronary angiographic findings and risk factors between the new immigrants and local Jewish and Arab patients in this era of cost containment. METHODS AND RESULTS: A total of 550 consecutive patients--314 Jews, 95 new immigrants and 141 Arabs--were catheterized and analyzed during a 5 month period in 1995. Of this group 403 were males (73%). The mean age was 63.6 +/- 10.2 years among new immigrants, 62.4 +/- 9.4 among Jews, and 55.1 +/- 10.9 among Arabs (P < 0.05). Immigrants, including those under age 60, had the highest prevalence of multivessel disease (88.7%). Arabs had a high prevalence of single vessel disease (34.6%) and a low prevalence of multivessel (65.4%) and left main coronary disease (5.6%). Age, gender, risk factors and ethnic origin in descending order were determinants of the extent of coronary angiographic disease as revealed by multiple regression analysis. CONCLUSION: New immigrants had the most extensive angiographic coronary involvement, while Arab patients were younger and had less severe coronary artery disease. More intensive risk factor modification may have a major impact on disease progression particularly in the new immigrant subgroup.  (+info)

Reaching the diagnosis of cystic fibrosis--the limits of the spectrum. (43/808)

BACKGROUND: Cystic fibrosis is the most common life-limiting autosomal recessive genetic disorder in Caucasians. Typically it is a multisystem disease diagnosed by increased chloride levels on sweat testing, with mortality due mainly to progressive respiratory disease. The clinical spectrum of CF has recently been much expanded. Genetic testing for mutant CF transmembrane regulator has revealed atypical cases where sweat test results are borderline or normal. In other patients, genetic mutations cannot be identified but abnormal CFTR function is shown using nasal potential difference measurement. OBJECTIVES: To highlight the diagnostic and therapeutic dilemmas in cases of atypical cystic fibrosis. METHODS: We reviewed patients with atypical CF and widely varying phenotype who are managed at Schneider Children's Medical Center of Israel. RESULTS: Two patients had severe lung disease but little expression in other organs. Accurate diagnosis was essential to enable aggressive therapy in a specialized center. Four other patients are in excellent general health but have symptoms limited to male infertility, heat exhaustion, pancreatitis or transient liver dysfunction, while lung disease is minimal. For these patients, careful counseling is needed to avoid unnecessary upheaval, inappropriately aggressive management, and the psychosocial implications of a CF diagnosis. These dilemmas have increased considerably in our center, as in others worldwide. CONCLUSION: It is our obligation as clinicians--at the level of both primary physician and referral center--to maintain an ever higher index of suspicion for CF, tempered by a rational program of counseling and management appropriate to the individual.  (+info)

Poison exposure in children before Passover. (44/808)

BACKGROUND: Extensive cleaning of homes in Israel before Passover may result in increased exposure of children to cleaning substances. OBJECTIVES: To evaluate the potential danger of Passover cleaning to children, and to study the risk factors in order to identify areas for prevention. METHODS: All cases of poison exposure in Jewish and Arab children under the age of 15 years reported to the Israel Poison Information Center during 1990-95 (n = 5,583) were analyzed for the 6 weeks before and 6 weeks after Passover. Poison exposures in Jewish children < 15 years old were studied in seven pediatric emergency rooms for the 2 weeks before and 6 weeks after Passover (n = 123). RESULTS: The IPIC data showed a highly significant 38% increase in the average weekly poison exposure rate for the 2 weeks before Passover compared with the remaining 10 weeks. Data recorded by the pediatric emergency rooms showed a twofold increase in cleaning substance poisoning during the 2 weeks before Passover compared with the following 6 weeks. The rise in exposures to cleaning substances was observed among children from secular, religious and ultra-orthodox families. In these exposures, the substance was found in open containers in 70% of cases. CONCLUSIONS: The extensive cleaning of homes among Jewish families in preparation for Passover poses the danger to young children of cleaning substance poisoning. Increasing public awareness, closer observation of children, and keeping these substances in closed containers should increase children's safety during this annual cleaning.  (+info)

Delayed growth and puberty in patients with Gaucher disease type 1: natural history and effect of splenectomy and/or enzyme replacement therapy. (45/808)

BACKGROUND: Growth retardation in childhood was only recently recognized as a prominent feature of Gaucher disease type 1, but there are few data on both the pubertal development and the final outcome of growth and sexual maturation. OBJECTIVE: To investigate the natural pattern of growth and puberty in patients with Gaucher disease type 1 and the effect of splenectomy and enzyme replacement therapy. METHODS: We retrospectively analyzed growth and puberty in 57 patients with Gaucher disease type 1; 52 were followed since childhood and/or prepuberty and 42 have reached sexual maturity and final height. In the analysis we considered severity of disease, time of splenectomy, and start of enzyme replacement therapy. RESULTS: Deceleration of growth at age 3-5 years was observed in 30 of 57 patients followed since early childhood while untreated: height-SDS decreased from -0.34 +/- 0.42 at age 0-3 years to -1.93 +/- 0.95 (P < 0.01) at age 7-10 years and was more pronounced with severe disease. A high prevalence (59.6%) of delayed puberty, which was more frequent with severe disease, was observed in 47 patients followed before and throughout puberty. No primary endocrine pathology was found. All patients, untreated as well as treated, with growth and pubertal delay had a spontaneous catch-up, achieved full sexual maturation, and most (83.3%) reached a final height within the range of parental height-standard deviation score. Splenectomy (partial and/or total) performed in 20 patients while still growing had a beneficial effect on growth, which was temporary in some and did not affect puberty. ERT improved growth in 11 patients who started therapy before puberty, as evidenced by a progressive increase in the height-SDS, and seemed to normalize the onset of puberty. CONCLUSIONS: Growth retardation in childhood and delay of puberty are characteristic of Gaucher disease type 1 and are more frequent with severe disease. There is a spontaneous catch-up later in life and most patients reach a final height within their genetic growth potential. Enzyme replacement therapy apparently normalizes growth and possibly also the onset of puberty.  (+info)

Primary node negative breast cancer in BRCA1 mutation carriers has a poor outcome. (46/808)

BACKGROUND: The association between BRCA1 germ-line mutations and breast cancer prognosis is controversial. A historical cohort study was designed to determine the prognosis for women with axillary lymph node negative hereditary breast cancer. PATIENTS AND METHODS: We tested pathology blocks from 118 Ashkenazi Jewish women with axillary lymph node negative breast cancer for the presence of the two common BRCA1 founder mutations, 185delAG and 5382insC. Patients were followed up for a median of 76 months. Somatic TP53 mutations were screened for by immunohistochemistry, and direct sequencing was performed in the BRCA1-positive tumours. RESULTS: Sixteen breast cancer blocks (13.6%) carried a BRCA1 mutation. Young age of onset, high nuclear grade, negative estrogen receptor status and over-expression of p53 were highly associated with BRCA1-positive status (P-values all <0.01). BRCA1 mutation carriers had a higher mortality than non-carriers (five-year overall survival, 50% and 89.6%, respectively, P = 0.0001). Young age of onset, estrogen receptor negative status, nuclear grade 3, and over-expression of p53 also predicted a poor outcome. Cox multivariate analyses showed that only germ-line BRCA1 mutation status was an independent prognostic factor for overall survival (P = 0.01). Among nuclear grade 3 tumours, the BRCA1 mutation carrier status was a significant prognostic factor of death (risk ratio 5.8, 95% confidence interval: 1.5-22, P = 0.009). Sequencing of BRCA1-related breast cancers revealed one TP53 missense mutation not previously reported in breast cancer. CONCLUSIONS: Using a historical cohort approach, we have identified BRCA1 mutation status as an independent prognostic factor for node negative breast cancer among the Ashkenazi Jewish women. Those managing women carrying a BRCA1 mutation may need take these findings into consideration. Additionally, our preliminary results, taken together with the work of others suggest a different carcinogenic pathway in BRCA1-related breast cancer, compared to non-hereditary cases.  (+info)

Muscular dystrophy due to dysferlin deficiency in Libyan Jews. Clinical and genetic features. (47/808)

The cluster in Jews of Libyan origin of limb-girdle muscular dystrophy type 2B due to a dysferlin 1624delG mutation is described. The carrier frequency of this mutation is calculated to be approximately 10% in this population, in which the disease prevalence is at least 1 per 1300 adults. Twenty-nine patients from 12 families were all homozygous for the same mutation. However, clinical features were heterogeneous even within the same family: in half of the patients onset was in the distal muscles of the legs, which is similar to Miyoshi myopathy, while in others onset was in the proximal musculature, which is similar to other forms of limb-girdle dystrophies. Age at onset varied from 12 to 28 years (mean 20.3 +/- 5.5 years). One patient was presymptomatic at age 28 years. Progression was slow regardless of age of onset, patients remaining ambulatory until at least 33 years. Five patients described subacute, painful enlarged calves as an early, unusual feature. The variable features in this ethnic cluster contribute to the definition of the clinical spectrum of dysferlinopathies in general. The cause of the observed heterogeneity remains unclear.  (+info)

XDH gene mutation is the underlying cause of classical xanthinuria: a second report. (48/808)

BACKGROUND: Classical xanthinuria is a rare autosomal recessive disorder characterized by excessive excretion of xanthine in urine. Type I disease results from the isolated deficiency of xanthine dehydrogenase (XDH), and type II results from dual deficiency of XDH and aldehyde oxidase. The XDH gene has been cloned and localized to chromosome 2p22-23. The aim of this study was to characterize the molecular basis of classical xanthinuria in an Iranian-Jewish family. METHODS: The apparently unrelated parents originated from a community in which consanguineous marriages are common. Subtyping xanthinuria was attempted by homozygosity mapping using microsatellite markers D2S352, D2S367, and D2S2374 in the vicinity of the XDH gene. Mutation detection was accomplished by PCR-SSCP screening of all 36 exons and exon-intron junctions of the XDH gene, followed by direct sequencing and confirmation of sequence alteration by restriction analysis. RESULTS: The index case was homozygous for all three microsatellite markers analyzed. The expected frequency of this genotype in a control population was 0. 0002. These results suggested that xanthinuria in the patient is linked to the XDH gene. Consequently, a 1658insC mutation in exon 16 of the XDH gene was identified. The 1658insC mutation was not detected in 65 control DNA samples. CONCLUSION: A molecular approach to the diagnosis of classical xanthinuria type I in a female patient with profound hypouricemia is described. Linkage of xanthinuria to the XDH locus was demonstrated by homozygosity mapping, and a 1658insC mutation, predicting a truncated inactive XDH protein, was identified. These results reinforce the notion that mutations in the XDH gene are the underlying cause of classical xanthinuria type I.  (+info)