Homozygous deletion in KVLQT1 associated with Jervell and Lange-Nielsen syndrome.
(9/6687)
BACKGROUND: Long-QT (LQT) syndrome is a cardiac disorder that causes syncope, seizures, and sudden death from ventricular arrhythmias, specifically torsade de pointes. Both autosomal dominant LQT (Romano-Ward syndrome) and autosomal recessive LQT (Jervell and Lange-Nielsen syndrome, JLNS) have been reported. Heterozygous mutations in 3 potassium channel genes, KVLQT1, KCNE1 (minK), and HERG, and the cardiac sodium channel gene SCN5A cause autosomal dominant LQT. Autosomal recessive LQT, which is associated with deafness, has been found to occur with homozygous mutations in KVLQT1 and KCNE1 in JLNS families in which QTc prolongation was inherited as a dominant trait. METHODS AND RESULTS: An Amish family with clinical evidence of JLNS was analyzed for mutations by use of single-strand conformation polymorphism and DNA sequencing analyses for mutations in all known LQT genes. A novel homozygous 2-bp deletion in the S2 transmembrane segment of KVLQT1 was identified in affected members of this Amish family in which both QTc prolongation and deafness were inherited as recessive traits. This deletion represents a new JLNS-associated mutation in KVLQT1 and has deleterious effects on the KVLQT1 potassium channel, causing a frameshift and the truncation of the KVLQT1 protein. In contrast to previous reports in which LQT was inherited as a clear dominant trait, 2 parents in the JLNS family described here have normal QTc intervals (0.43 and 0.44 seconds, respectively). CONCLUSIONS: A novel homozygous KVLQT1 mutation causes JLNS in an Amish family with deafness that is inherited as an autosomal recessive trait. (+info)
Influence of maternal ethnicity on infant mortality in Chicago, 1989-1996.
(10/6687)
This study compared infant mortality rates between large ethnic groups in Chicago from 1989-1996. Infant mortality information about ethnic groups was compared using data from annual reports published by the Epidemiology Program, Department of Public Health, City of Chicago and vital statistics documents in Illinois, which include information on ethnicity. Chi-squared analysis was used to evaluate the differences between the proportions. A P value of < .05 was considered significant. During the study period, there were 461,974 births and 6407 infant deaths in Chicago. African Americans contributed 212,924 (46.1%) births and 4387 (68.5%) deaths; Hispanics 132,787 (28.7%) births and 1166 (18.2%) deaths; and whites 99,532 (21.6%) births and 780 (12.2%) infant deaths. Compared with the other groups. African Americans suffered a twofold increased mortality (P < .00001) for five of the six most common causes of infant mortality. Deaths from congenital malformations, although significant, were not excessively increased among African Americans (P = .014). Hispanics demonstrated a higher mortality rate than whites (P = .01), especially for postnatal mortality and respiratory distress syndrome. These data confirm excessive infant mortality among African Americans. Further studies are needed to evaluate the apparent low mortality among some Hispanics compared with the other groups studied. (+info)
Feasibility of finding an unrelated bone marrow donor on international registries for New Zealand patients.
(11/6687)
Allogeneic bone marrow transplantation is the treatment of choice for several hematological conditions. Unfortunately, for the majority (70%) of patients an HLA-matched sibling donor is not available and a matched unrelated donor must be found if they are to proceed to allogeneic transplantation. Most of the donors on international registries are of Caucasian ethnic origin. It has been recognized that patients from certain racial groups have a reduced chance of finding an unrelated donor. This study reports the feasibility of finding an unrelated donor for our local New Zealand patients of Caucasian, New Zealand Maori and Pacific Islander ethnic origin presenting with transplantable hematological conditions at a single center. The search was performed on international registries using HLA-A,B and DR typings for our patients. Six of six and five of six matches were evaluated. We have shown that Maori and Pacific Islanders have significantly lower hit rates than Caucasians when searched for 6/6 antigen matches, but there was no significant difference between the three ethnic groups in finding a 5/6 antigen matched donor. This study supports the policy of the New Zealand Bone Marrow Donor Registry in recruiting New Zealand Maori and Pacific Islanders. (+info)
Cigarette smoking and other risk factors in relation to p53 expression in breast cancer among young women.
(12/6687)
p53 mutations may be a fingerprint for cigarette smoking and other environmental carcinogens, including breast carcinogens. This study was undertaken to explore whether p53 mutations are associated with environmental or other suspected or established risk factors for breast cancer. p53 protein detection by immunohistochemistry (which is more easily quantified in large epidemiological studies than are mutations, and are highly correlated with them) was determined for 378 patients from a case-control study of breast cancer. In this population-based sample of women under the age of 45 years, 44.4% (168/378) of the cases had p53 protein detected by immunohistochemistry (p53+). Polytomous logistic regression was used to calculate the odds ratios (ORs) for p53+ and p53- breast cancer, as compared with the controls, in relation to cigarette smoking and other factors. The ratio of the ORs was used as an indicator of heterogeneity in risk for p53+ versus p53- cancer. The ratio of the ORs in a multivariate model was substantially elevated among women with a greater than high school education [2.39; 95% confidence interval (CI), 1.43-4.00], current cigarette smokers (1.96; 95% CI, 1.10-3.52), and users of electric blankets, water beds, or mattresses (1.78; 95% CI, 1.11-2.86). Nonsignificant heterogeneity was noted for family history of breast cancer and ethnicity but not for other known or suspected risk factors. Coupled with the strong biological plausibility of the association, our data support the hypothesis that in breast cancer, as with other tumors, p53 protein immunohistochemical detection may be associated with exposure to environmental carcinogens such as cigarette smoking. (+info)
Pterygium and its relationship to the dry eye in the Bantu.
(13/6687)
A comparative study was performed on two groups of Bantus in Johannesburg to see if there was any relationship between the "dry eye" and pterygia, but no correlation was found. (+info)
Analysis of chromosome 1q42.2-43 in 152 families with high risk of prostate cancer.
(14/6687)
One hundred fifty-two families with prostate cancer were analyzed for linkage to markers spanning a 20-cM region of 1q42.2-43, the location of a putative prostate cancer-susceptibility locus (PCAP). No significant evidence for linkage was found, by use of both parametric and nonparametric tests, in our total data set, which included 522 genotyped affected men. Rejection of linkage may reflect locus heterogeneity or the confounding effects of sporadic disease in older-onset cases; therefore, pedigrees were stratified into homogeneous subsets based on mean age at diagnosis of prostate cancer and number of affected men. Analyses of these subsets also detected no significant evidence for linkage, although LOD scores were positive at higher recombination fractions, which is consistent with the presence of a small proportion of families with linkage. The most suggestive evidence of linkage was in families with at least five affected men (nonparametric linkage score of 1.2; P=.1). If heterogeneity is assumed, an estimated 4%-9% of these 152 families may show linkage in this region. We conclude that the putative PCAP locus does not account for a large proportion of these families with prostate cancer, although the linkage of a small subset is compatible with these data. (+info)
Molecular analysis of the ERGIC-53 gene in 35 families with combined factor V-factor VIII deficiency.
(15/6687)
Combined factor V-factor VIII deficiency (F5F8D) is a rare, autosomal recessive coagulation disorder in which the levels of both coagulation factors V and VIII are diminished. The F5F8D locus was previously mapped to a 1-cM interval on chromosome 18q21. Mutations in a candidate gene in this region, ERGIC-53, were recently found to be associated with the coagulation defect in nine Jewish families. We performed single-strand conformation and sequence analysis of the ERGIC-53 gene in 35 F5F8D families of different ethnic origins. We identified 13 distinct mutations accounting for 52 of 70 mutant alleles. These were 3 splice site mutations, 6 insertions and deletions resulting in translational frameshifts, 3 nonsense codons, and elimination of the translation initiation codon. These mutations are predicted to result in synthesis of either a truncated protein product or no protein at all. This study revealed that F5F8D shows extensive allelic heterogeneity and all ERGIC-53 mutations resulting in F5F8D are "null." Approximately 26% of the mutations have not been identified, suggesting that lesions in regulatory elements or severe abnormalities within the introns may be responsible for the disease in these individuals. In two such families, ERGIC-53 protein was detectable at normal levels in patients' lymphocytes, raising the further possibility of defects at other genetic loci. (+info)
Cardiovascular mortality of Chinese in New York City.
(16/6687)
To determine cardiovascular disease mortality among Chinese migrants in New York City and compare it to both that of residents in China and whites in New York City, mortality records for 1988 through 1992 for New York City and the 1990 US census data for New York City were linked. Age-specific death rates for urban China, reported by the World Health Organization, were used for comparison. The results show that male and female Chinese residents in New York City had lower mortality rates for all causes and total cardiovascular disease than did either New York City whites or Chinese in China. Coronary heart disease deaths among New York City Chinese were intermediate between Chinese in China (lowest) and New York City whites (highest). Stroke death rates for New York City Chinese were substantially lower than those in China and, in general, were similar to those for New York City whites. However, New York City Chinese had higher death rates for hemorrhagic stroke and lower for atherosclerotic stroke than did New York City whites. In conclusion, cardiovascular mortality rates among Chinese migrants in New York City fall below those of both Chinese in China and whites in New York City. (+info)