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Diego F Wyszynski

Publications and source records attributed to Diego F Wyszynski.

35 records · Page 2Linked to original sources
PubMed2004

Feasibility of identifying families for genetic studies of birth defects using the National Health Interview Survey.

BACKGROUND: The purpose of this study was to determine whether the National Health Interview Survey is a useful source to identify informative families for genetic studies of birth defects. METHODS: The 1994/1995 National Health Interview Survey (NHIS) was used to identify households where individuals with two or more birth defects reside. Four groups of households were identified: 1) single non-familial (one individual with one birth defect); 2) single familial (more than one individual with one birth defect); 3) multiple non-familial (one individual with more than one birth defect), and 4) multiple familial (more than one individual with more than one birth defect). The March 2000 U.S. Census on households was used to estimate the total number of households in which there are individuals with birth defects. RESULTS: Of a total of 28,094 households and surveyed about birth defects and impairments, 1,083 single non-familial, 55 multiple non-familial, 54 single familial, and 8 multiple familial households were identified. Based on the 2000 U.S. census, it is estimated that there are 4,472,385 households where at least one person has one birth defect in the United States and in 234,846 of them there are at least two affected individuals. Western states had the highest prevalence rates. CONCLUSIONS: Population-based methods, such as the NHIS, are modestly useful to identify the number and the regions where candidate families for genetic studies of birth defects reside. Clinic based studies and birth defects surveillance systems that collect family history offer better probability of ascertainment.

Age Distribution↗
PubMed2004

The AED (antiepileptic drug) pregnancy registry: a 6-year experience.

BACKGROUND: Pregnancy registries are a new method for assessing the fetal risks from exposures in pregnancy. We present the findings of the North American AED (antiepileptic drug) Pregnancy Registry for phenobarbital sodium-exposed pregnancies. OBJECTIVE: To determine whether exposure during pregnancy to anticonvulsant drugs as monotherapy, and phenobarbital in particular, is associated with an increased risk of major malformations in comparison with unexposed controls. DESIGN: Evaluation of registry data. SETTING: The North American AED Pregnancy Registry. PATIENTS: Pregnant women throughout the United States and Canada who were taking an anticonvulsant drug and who called a toll-free telephone number to enroll. INTERVENTIONS: Each woman was interviewed by telephone at enrollment, at 7 months' gestation, and post partum. With the mother's written permission, her medical records and those of her infant were obtained. MAIN OUTCOME MEASURES: Major malformations identified by 5 days of age. Criteria for the release of findings were established by the independent Scientific Advisory Committee on the basis of malformations identified in infants of women who had enrolled prospectively before having had any prenatal screening ("pure" enrollees). RESULTS: Five (6.5%) of 77 pure pregnancies with exposure to phenobarbital monotherapy were associated with major malformations (95% confidence interval of proportion, 2.1%-14.5%). When compared with the background rate (1.62%), there was a significantly increased risk (relative risk, 4.2; 95% confidence interval, 1.5-9.4). CONCLUSIONS: A hospital-based pregnancy registry can establish the fetal risk of major malformations for a commonly used drug. Prenatal exposure to phenobarbital is associated with a significantly increased risk of fetal abnormalities.

Abnormalities, Drug-Induced↗
PubMed2003

Search for genetic factors predisposing to atherogenic dyslipidemia.

BACKGROUND: Atherogenic dyslipidemia (AD) is a common feature in persons with premature coronary heart disease. While several linkage studies have been carried out to dissect the genetic etiology of lipid levels, few have investigated the AD lipid triad comprising elevated serum triglyceride, small low density lipoprotein (LDL) particles, and reduced high density lipoprotein (HDL) cholesterol levels. Here we report the results of a whole-genome screen for AD using the Framingham Heart Study population. RESULTS: Our analyses provide some evidence for linkage to AD on chromosomes 1q31, 3q29, 10q26, 14p12, 14q13, 16q24, 18p11, and 19q13. CONCLUSION: AD susceptibility is modulated by multiple genes in different chromosomes. Our study confirms results from other populations and suggests new areas of potential importance.

Adult Children↗
PubMed2003

Genome-wide screen for heavy alcohol consumption.

BACKGROUND: To find specific genes predisposing to heavy alcohol consumption (self-reported consumption of 24 grams or more of alcohol per day among men and 12 grams or more among women), we studied 330 families collected by the Framingham Heart Study made available to participants in the Genetic Analysis Workshop 13 (GAW13). RESULTS: Parametric and nonparametric methods of linkage analysis were used. No significant evidence of linkage was found; however, weak signals were identified in several chromosomal regions, including 1p22, 4q12, 4q25, and 11q24, which are in the vicinity of those reported in other similar studies. CONCLUSION: Our study did not reveal significant evidence of linkage to heavy alcohol use; however, we found weak confirmation of studies carried out in other populations.

Adult Children↗
PubMed2003

Empirically derived phenotypic subgroups - qualitative and quantitative trait analyses.

BACKGROUND: The Framingham Heart Study has contributed a great deal to advances in medicine. Most of the phenotypes investigated have been univariate traits (quantitative or qualitative). The aims of this study are to derive multivariate traits by identifying homogeneous groups of people and assigning both qualitative and quantitative trait scores; to assess the heritability of the derived traits; and to conduct both qualitative and quantitative linkage analysis on one of the heritable traits. METHODS: Multiple correspondence analysis, a nonparametric analogue of principal components analysis, was used for data reduction. Two-stage clustering, using both k-means and agglomerative hierarchical clustering, was used to cluster individuals based upon axes (factor) scores obtained from the data reduction. Probability of cluster membership was calculated using binary logistic regression. Heritability was calculated using SOLAR, which was also used for the quantitative trait analysis. GENEHUNTER-PLUS was used for the qualitative trait analysis. RESULTS: We found four phenotypically distinct groups. Membership in the smallest group was heritable (38%, p < 1 x 10(-6)) and had characteristics consistent with atherogenic dyslipidemia. We found both qualitative and quantitative LOD scores above 3 on chromosomes 11 and 14 (11q13, 14q23, 14q31). There were two Kong & Cox LOD scores above 1.0 on chromosome 6 (6p21) and chromosome 11 (11q23). CONCLUSION: This approach may be useful for the identification of genetic heterogeneity in complex phenotypes by clarifying the phenotype definition prior to linkage analysis. Some of our findings are in regions linked to elements of atherogenic dyslipidemia and related diagnoses, some may be novel, or may be false positives.

Adult Children↗
PubMed2003

A genome-wide scan for loci predisposing to non-syndromic cleft lip with or without cleft palate in two large Syrian families.

Non-syndromic cleft lip with/without cleft palate (CL/P) is a common, usually non-fatal birth defect of complex etiology. Several segregation analyses have demonstrated that genetic factors are important in the pathogenesis of CL/P, most likely through the interaction of several genes of modest effects. The aim of this study was to perform a genome-wide linkage analysis to identify/search for candidate gene loci for CL/P. We conducted a genome-wide search in two large, relatively isolated Syrian families, each one with a large number of cases with CL/P (18 in family 1 and 4 in family 2). A locus with a multipoint LOD score of 2.80 and a 2-point non-parametric MLS LOD of 3.0 was detected on 17p13.1. Other chromosomal regions with multipoint LOD scores > or = 1.2 (P < or = 0.01) included 3p21.2, 4q32.1, and 7q34. These data indicate the possible presence of several susceptibility loci for CL/P and identify a strong candidate locus for this common birth defect on chromosome 17p13.

Chromosome Mapping↗
PubMed2003

Analysis of metabolic syndrome phenotypes in Framingham Heart Study families from Genetic Analysis Workshop 13.

Twelve teams of investigators constituted a group which analyzed phenotypes related to metabolic syndrome, making use of the available longitudinal measurements from the family component of the Framingham Heart Study or the simulated data, as distributed by Genetic Analysis Workshop 13 (GAW13). Body mass index, obesity, lipid abnormalities, glucose, or combinations of these traits were analyzed by this group. A wide variety of approaches were taken to construct phenotypes from the longitudinal measurements, including considering single or multiple cross-sectional time points, single ages, minimum values, maximum values, means, other lifetime values, ever/never dichotomy, or age at onset of some threshold value. Approaches also differed in the family structures utilized (sib pairs to full extended pedigrees), the genetic data considered (two-point or multipoint), and the statistics calculated (model-free and parametric), and led to a diverse set of analyses being performed. Inferences were made about heritability, and attempts were made to map underlying genes. Over 40 genome-wide linkage analyses were conducted. Despite the broad range of approaches, several regions of the genome were repeatedly identified across multiple analyses.

Cardiovascular Diseases↗
PubMed2003

Attitudes toward prenatal diagnosis, termination of pregnancy, and reproduction by parents of children with nonsyndromic oral clefts in Argentina.

OBJECTIVE: To investigate the attitudes of Argentine parents of children with nonsyndromic oral clefts with respect to prenatal diagnosis, termination of pregnancy, and reproduction and to assess the variables that might influence their responses. DESIGN: One hundred and sixty-five parents of children with oral clefts, ascertained from a craniofacial clinic in the suburbs of Buenos Aires, answered a 151-item semistructured questionnaire. The questionnaire included sections covering sociodemographic information, level of religiousness, characteristics of the child's cleft, parental perception of their child's cleft, pregnancy history, recurrence risk, access to health care, attitudes in regard to abortion, and family environment. RESULTS: Most parents (60%) believe their child's cleft is not a serious condition. None of the respondents would terminate a pregnancy because the ultrasound reveals an oral cleft. Similarly, very few (6.1%) would terminate the pregnancy if there were an early diagnosis of Down syndrome. Half of the respondents believe that abortion should not be an option for any couple expecting a child. CONCLUSIONS: Most respondents do not perceive oral clefts as a severe condition. Parents would not choose to terminate the pregnancy over delivery of such an affected newborn.

Abortion, Induced↗
PubMed2003

Protective effect of hyperemesis gravidarum for nonsyndromic oral clefts.

OBJECTIVE: To evaluate whether hyperemesis gravidarum is associated with a decreased risk for nonsyndromic oral clefts and to examine the relationship between hyperemesis gravidarum, birth weight, and gestational age. METHODS: This was a population-based, matched case-control study of 1950 subjects with oral clefts (1368 with cleft lip with or without cleft palate; 582 with cleft palate) collected from the Hungarian Congenital Abnormality Registry and 1955 controls identified from the National Birth Registry. RESULTS: Fewer mothers of newborns with oral clefts had early-onset hyperemesis gravidarum than did mothers of controls (cleft lip with or without cleft palate: 83 cases and 121 controls, odds ratio [OR] = 0.67, 95% confidence interval [CI] 0.50, 0.89; cleft palate: 42 cases and 64 controls, OR = 0.63, 95% CI 0.42, 0.94). The use of dimenhydrinate was more common among mothers of subjects with cleft palate (OR = 2.47, 95% CI 1.11, 5.49), whereas iron seemed to have a protective effect against this condition (OR = 0.26, 95% CI 0.09, 0.80). Gestational age and birth weight were not significantly associated with hyperemesis gravidarum. CONCLUSION: This study suggests that hyperemesis gravidarum provides a protective effect against risk to oral clefts in newborns.

Adult↗
PubMed2003

Prevalence of hospital malnutrition in Argentina: preliminary results of a population-based study.

OBJECTIVE: We investigated the prevalence of malnutrition in a sample of hospitalized patients in Argentina. METHODS: A random population-based sample of 1000 inpatients in 38 hospitals in 17 cities of Argentina was selected and studied with the Subjective Global Assessment (physical examination plus questionnaire). RESULTS: Forty-seven percent of the participants were identified as having some degree of malnourishment, one-fourth of which was considered severe. Older males, especially those with cancer or infections, were at highest risk. Nutritional information was incorporated into the patients' charts in only 38.8% of cases, and fewer than 15% had records of usual or current weight and height. CONCLUSIONS: This study suggested that malnutrition among hospital inpatients in Argentina is common and that the patients' nutrition status is largely unrecognized and neglected in their hospital charts.

Aged↗
PubMed2003

Evidence for linkage of nonsyndromic cleft lip with or without cleft palate to a region on chromosome 2.

Results from a genome-wide screen of 10 multiplex families ascertained through probands with nonsyndromic cleft lip with or without cleft palate (CL/P) in Mexico, Argentina, and the United States yielded suggestive evidence of linkage to chromosomes 2, 6, 17 and 18. Fine mapping excluded all regions except chromosome 2. Subsequent analysis was performed on the original 10 families plus an additional 16 families using 31 markers on chromosome 2. This analysis showed intriguing evidence of linkage to 2q (Zlr=2.26, empirical P-value=0.028 in a chromosome-wide analysis). Transmission disequilibrium tests also revealed evidence of linkage and disequilibrium for two markers in this region (D2S168 and D2S1400 with P-values=0.022 and 0.006, respectively). A subset of these 26 families provided additional evidence for a susceptibility gene for CL/P on 2q, suggesting that further studies of genes in this region are warranted.

Chromosome Mapping↗
PubMed2003

Birth weight and gestational age of newborns with cleft lip with or without cleft palate and with isolated cleft palate.

The birth weight and gestational age of 1368 newborns with isolated cleft lip with or without cleft palate and 582 with isolated cleft palate were compared to those of matched healthy controls. The results indicate that fetuses with oral clefts are at elevated risk of having low and very low birth weight, but not of having a premature birth. Speculations on a relationship between these findings and the presence of oral clefts are presented.

Adult↗
PubMed2002

Guidelines for the design and analysis of studies on nonsyndromic cleft lip and cleft palate in humans: summary report from a Workshop of the International Consortium for Oral Clefts Genetics.

OBJECTIVE: The members of the International Consortium for Oral Clefts Genetics recognize the need for collaboration between researchers involved in etiologic studies of nonsyndromic cleft lip and palate and cleft palate. To address this need, the consortium established four working subcommittees: diagnostic and phenotypic assessment, molecular genetic studies, epidemiologic data collection and analysis, and genetic data collection and analysis. These subcommittees were charged with the development of guidelines for data collection and analysis that would facilitate both a priori and a posteriori comparisons and pooling of data from multiple centers. This report presents summary statements of the four subcommittees.

Cleft Lip↗
PubMed2002

Use of US birth certificate data to estimate the risk of maternal cigarette smoking for oral clefting.

OBJECTIVE: The purpose of this study was to evaluate the relationship between maternal cigarette smoking and the risk of having an offspring with an oral cleft. DESIGN: This was a large population-based, matched case-control study derived from the United States Natality database for 1997. SUBJECTS: The sample consisted of 2029 cases with non-syndromic oral clefts and 4050 non-malformed controls. Controls were matched to cases on mother's and father's race and child's sex, county of birth, and month of birth. This sample was selected from a total of 3,093,821 births in the United States, which represents 80% of all births in this country during 1997. RESULTS: The association between maternal cigarette smoking and oral clefts in the offspring was close to the null (odds ratio 1.16; 95% confidence interval (CI) 1.01 to 1.33; one-sided Fisher exact test p =.0207). The comparison and pooling of results to those of a similar study that used the U.S. Natality database for 1996 resulted in a common Mantel-Haenszel odds ratio of 1.33 (95% CI 1.21 to 1.46). The dose-response analysis was slightly significant for all levels of maternal smoking. CONCLUSION: This large study confirms that smoking during pregnancy is only a minor risk factor for oral clefting in the offspring.

Adult↗
PubMed2002

Prenatal and perinatal factors associated with isolated oral clefting.

OBJECTIVE: To describe medical service utilization and maternal morbid conditions of women who carry offspring with oral clefts (OCs), to describe maternal and offspring complications during birth, and to evaluate postnatal characteristics of their newborns with isolated OCs. METHODS: Two thousand four hundred thirty-seven patients with isolated OCs and 4871 unaffected matched controls meeting inclusion criteria were selected from the U.S. Natality database for 1997. Matching variables were mother's and father's race and child's race, sex, county of birth, and month of birth. Patients and controls were compared in terms of maternal demographic characteristics, gestational complications, physical characteristics of the newborns, maternal exposure to potential risk factors, and adequacy of prenatal care. RESULTS: Although the quality of care was very good in both groups, low gestational age, low birth weight, and low 5-minute Apgar score are more frequent among newborns with OCs than in unaffected controls. Mothers of offspring with OCs are at increased risk, compared with mothers of controls, of having hydramnios or oligohydramnios, eclampsia, and abruptio placenta. Obstetric procedures, such as amniocentesis, electronic fetal monitoring, induction of labor, tocolysis, and ultrasound, and repeat cesarean deliveries are more frequent among mothers of patients than those of controls. At birth, newborns with isolated OCs are at risk of having hyaline membrane disease and of requiring assisted ventilation, independently of gestational age. CONCLUSION: The results of this large population-based, case-control study suggest that the presence of an OC in the offspring is associated with increased risk for prenatal and perinatal complications in the mother.

Abruptio Placentae↗