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Biomedical subjects

W E Nance

Publications and source records attributed to W E Nance.

At least 73 records · Page 4Linked to original sources
PubMed1987

Goldenhar complex in discordant monozygotic twins: a case report and review of the literature.

In 1952, Goldenhar described a pair of monozygotic twins who were discordant for epibulbar dermoids, auricular appendages, malformations of the auricle, and hemifacial microsomia. Eighteen twin pairs have subsequently been described in which at least one member exhibited these manifestations. We report on an additional pair of discordant dichorionic monozygotic male twins. All of the 5 monozygotic twin pairs for which placental information is available have been discordant and 2 of these had dichorionic membranes. The failure of discordant monozygotic twins to be limited to monochorionic pairs argues against the hypothesis that developmental abnormalities arising from the placental vascular anastomoses that are commonly found in monozygotic twins is the probable explanation for the discordant expression of these traits in twins.

Female↗
PubMed1987

Early onset periodontitis: a comparison and evaluation of two proposed modes of inheritance.

Two rare types of familial periodontitis, a localized form usually diagnosed in late adolescence, and a more generalized form with a latter mean age of diagnosis, have been analyzed with respect to genetic models currently favored in the dental literature. These include autosomal recessive and X-linked dominant (partial penetrance) inheritance. Since there is variation in severity, extent, age of onset, altered sex ratio of affected individuals, and a low population prevalence, it is not surprising that genetic mechanisms heretofore have not been revealed. We have compared the likelihoods of 33 kindreds ascertained through affected probands under the above genetic models. Our findings include (1) several families in which both forms of early onset periodontitis co-occur, making it unlikely that the clinical varieties of the disease have unrelated genetic causes; (2) the autosomal recessive model is far more likely than the X-linked dominant model. The superiority of the recessive hypothesis arises from the fact that there are only a few instances of affected individuals having affected parents and because the skewed sex ratio is shown to be incompatible with X-linked inheritance. These conclusions are largely insensitive to the assumptions of the analysis. We conclude that the X-linked dominant hypothesis is inadequate, and while the autosomal recessive model is by no means proven, it is clearly favored.

Adolescent↗
PubMed1987

The influence of secular effects and gravidity on the rate of ectopic pregnancy in a Norwegian population.

In order to assess the influence of secular effects and gravidity on the incidence rate of ectopic pregnancy, information from reproductive history questionnaires was obtained for 7804 gravid females identified through the Norwegian Twin Panel. The overall ectopic pregnancy incidence rate was 5.6 per 1000 estimated conceptions, with rates increasing for women born after 1950. Women experiencing their first pregnancy were at lowest risk for that pregnancy being ectopic. When women were stratified by whether they were born before or after 1950, gravidity still had an effect on the incidence rate of ectopic pregnancy. Conversely, year of birth was influential when stratifying by gravidity. The results obtained here suggest that the recent increase in the incidence of ectopic pregnancy is unrelated to the number of prior pregnancies.

Diseases in Twins↗
PubMed1987

The effect of perinatal screening in Norway on the magnitude of noninherited risk factors for congenital dislocation of the hip.

Several investigators have noted an increase in the rate of congenital dislocation of the hip shortly after the initiation of neonatal screening procedures. This increase has been attributed to the detection of temporarily unstable hips which require no corrective treatment. To test whether neonatal screening had low specificity, the authors obtained data on 17,145 offspring of 7,896 twins from the Norwegian Twin Panel. Information from maternal reproduction history questionnaires was available on the presence or absence of congenital dislocation of the hip, type of obstetric delivery, and parity. The reported prevalence of the disorder did indeed begin to rise sharply during the late 1950s, at which time neonatal screening started in Norway. Infants were then grouped by year of birth (born before or after 1960), and odds ratios were calculated for breech delivery and early (first or second) parity. For the pre-screening group, the odds ratio of congenital dislocation of the hip was 7.7 among children delivered by breech presentation and 2.6 among those of early parity. These values are similar to those found in other studies. In the post-screening group, the odds ratios for breech delivery and early parity were 1.5 and 1.2, respectively. Breech delivery and early parity have been consistent risk factors for congenital dislocation of the hip. Their diminished influence in the post-screening group, as well as sharply increased rates of the disorder, suggests that in Norway neonatal screening programs may have had low specificity in detecting cases that required treatment.

Cross-Sectional Studies↗
PubMed1987

Does the PI polymorphism alone control alpha-1-antitrypsin expression?

Whether genetic factors other than the protease-inhibitor (PI) polymorphism itself contribute to variation in alpha-1-antitrypsin is of both theoretical and practical interest. We have measured the quantity of alpha-1-antitrypsin (by an immunoturbidometric assay) and its activity (by assaying elastase inhibitory capacity [EIC]) in 583 individuals from 114 twin kinships who were also typed for PI by isoelectric focusing. Models of variation were fitted directly to the raw observations by a maximum-likelihood method. Specification of phenotypic means led to highly significant improvements in fit over models including only individual environment variance and additive genetic variance. The 29 phenotype means could also be described as the appropriate additive combinations of the 12 allelic effects. Only small improvements in fit could then be obtained by addition of polygenic components of variance. We conclude that nearly all genetic variation in alpha-1-antitrypsin quantity and activity can be explained by detectable variation at the PI locus and that this variance is largely additive. Bivariate analysis of alpha-1-antitrypsin and EIC revealed marginal evidence for differences in specific activities of molecules coded by different PI alleles. The correlation between environmental deviations for the two measures was only .63, which may reflect, in part, the rather low reliability of the assays and account for the modest heritabilities (less than .5) of the two measures. An intriguing finding was the presence of significant differences in E1 variance for different PI types, suggesting that different phenotypes have differing capacities to react to environmental challenges.

Adolescent↗
PubMed1987

High-density lipoprotein-cholesterol subfractions in adolescent twins.

Data on the levels of high-density lipoprotein-cholesterol (HDL-C) and subfractions in 102 adolescent twin pairs and their parents are presented. Children with a family history of premature cardiovascular death had lower levels of HDL2-C than did those without such a history. White girls reporting a high level of physical activity had higher levels of HDL-C and HDL2-C than did their more sedentary peers. In general, children of mothers who smoked had lower HDL2-C than did children of nonsmoking mothers. These findings suggest that low levels of HDL2-C in children may identify families in which there is an increased risk of coronary heart disease and that parental smoking may contribute to changes in this risk factor in the children of smokers as well as in the smokers themselves.

Adult↗
PubMed1986

Updating McKusick: an educational exercise for medical students.

An educational module is described in which first-year medical students were assigned different entries from the 1983 edition of McKusick's Mendelian Inheritance in Man to revise and update. Following review and discussion in small group sections, the entries were reproduced to provide each student with an updated compendium of the selected genetic disorders. The important principles of Mendelian inheritance could be readily illustrated by the entities assigned to each discussion group. Students learned to use the library and how to understand and integrate clinical and experimental papers. More than half the students reported spending 11-20 h to complete the assignment and reviewed from six to ten articles in detail. The caliber of the entries was found to be significantly correlated with the time students reported they spend on the exercise, but not with the number of papers reviewed, prior knowledge of the disease entity, the frequency of dictionary usage, or undergraduate exposure to genetics.

Education, Medical, Undergraduate↗
PubMed1986

Testing for developmental changes in gene expression on resemblance for quantitative traits in kinships of twins: application to height, weight, and blood pressure.

Height, weight, and blood pressure measurements on identical and fraternal twins and their families were analyzed to assess the degree to which genetic effects may change with age. The blood pressure data were based on the total sample of 1,767 individuals, while height and weight were available on 1,640 individuals in 204 monozygotic twin kinships. The results of testing alternative hypotheses about developmental changes in gene expression indicate that different mechanisms may be operative for these traits. While there was no evidence that developmental effects are a significant source of the observed variation in systolic or diastolic blood pressure, there was strong evidence that genetically determined developmental changes are an important factor in the determination of body weight. Age-related changes in weight appeared to be best explained by the cumulative developmental effects of a single set of genes, rather than by the expression of new genes at different stages of development.

Adolescent↗
PubMed1986

Neonatal screening for biotinidase deficiency: results of a 1-year pilot study.

We screened 81,243 infants born in Virginia during the 1-year period beginning Jan. 24, 1984, for deficiency of the enzyme biotinidase. A simple colorimetric screening procedure was used to detect the presence or absence of biotinidase activity on the same blood-soaked filter paper cards that are currently used in most neonatal metabolic screening programs. Two newborn infants with biotinidase deficiency were identified during the 12-month pilot study. In addition, two affected siblings of one of the newborn infants were detected through secondary family screening. On the basis of these results, the disorder appears to be at least as frequent as several others for which newborn screening is currently conducted. There were no known false-negative test results, and only 0.09% false-positive results that necessitated requests for second blood samples. False-positive test results can be readily identified by the use of a quantitative assay, which can also be used to confirm the diagnosis and to detect heterozygous family members in the case of true positives. On the basis of currently recognized criteria, biotinidase deficiency should be considered for inclusion among the metabolic disorders for which screening is performed in the neonatal period.

Age Factors↗
PubMed1986

Detection and localization of an extra HLA locus in a karyotypically normal male by chromosomal in situ hybridization.

The codominant expression of three HLA haplotypes was found in a healthy 21-year-old Black male, whose prometaphase karyotype was normal by light microscopy. He was the sibling of an antenatally diagnosed female fetus with a partial duplication of 6p. The duplication arose from a complex presumably balanced maternal chromosome rearrangement: 46,XX,dir ins(14;6)(14pter----14p11::6p22----6p21.1::14 p11----14qter; 6pter----6p22::6p21.1----6qter). Chromosomal in situ hybridization using a tritium-labeled genomic clone corresponding to a class I HLA gene revealed two sites of hybridization: at 6p21.3, the band to which this probe has been assigned in normal individuals (Morton et al. 1984a) and a second site at 6p11. We postulate that a recombinational event during meiotic pairing in the mother led to the reintroduction into the normal chromosome 6 homolog of a small segment of the original insertion in chromosome 14 which contained the HLA-A and -B determinants.

Chromosome Banding↗
PubMed1985

Clinical findings in four children with biotinidase deficiency detected through a statewide neonatal screening program.

Four children with biotinidase deficiency were identified during the first year of a neonatal screening program for this disease in the Commonwealth of Virginia. Two unrelated probands were identified among the 81,243 newborn infants who were screened. In addition, two siblings of one of these infants were found to be affected. Both probands had mild neurologic symptoms at two and four months, respectively, and the two older children had more severe neurologic abnormalities, cutaneous findings, and developmental delay at two and three years of age. However, none of the affected children had acute metabolic decompensation. Previous studies have shown that the administration of biotin to affected children can be a lifesaving procedure that can reverse acute symptoms and prevent irreversible neurologic damage. Our findings demonstrate that subtle neurologic abnormalities may appear as early as at two months of age and that developmental abnormalities may occur even in the absence of episodes of overt metabolic decompensation. Since screening and treatment are both inexpensive and effective and the incidence of the disease is well within the range of that of other metabolic diseases for which screening is performed, biotinidase deficiency should be added to the group of metabolic diseases for which screening is done in the neonatal period.

Amidohydrolases↗
PubMed1985

Prediction of carrier status in Duchenne dystrophy by creatine kinase measurement.

Serum creatine kinase (CK) was measured in 515 healthy white women and 28 obligate carriers for Duchenne muscular dystrophy. There was substantial overlap between the control and carrier populations. To analyze the impact of the degree of overlap, the predictive value of a CK result was determined by (1) using sensitivity and specificity analysis, which assumes dichotomization into a positive or negative result based on a particular cut-off value; and (2) using likelihood ratio analysis, which evaluates an individual result based on the continuum observed for control and carrier populations. There was no clinically important difference whether an observed 57% or a hypothetical 33% overlap between control and carrier results was used. Because of the substantial overlap, the CK test utility is limited to those suspected carriers whose results fall above the healthy population interval. A low CK result does not provide sufficient assurance of noncarrier status.

Adult↗
PubMed1985

The heritability of smoking behaviour in pregnancy, and the birth weights of offspring of smoking-discordant twins.

Questionnaire information on smoking habits in pregnancy was collated in 341 monozygotic (MZ) and 321 dizygotic (DZ) female twin pair cases from a population-based Norwegian Twin Panel. In a multifactorial model, the intra-pair correlation in smoking was 0.797 (+/- 0.042) in monozygotic (MZ) and 0.443 (+/- 0.075) in dizygotic (DZ) twin pairs, indicating a substantial genetic influence on liability to smoke in pregnancy. The questionnaire information was linked with birth records in the Medical Birth Registry of Norway, and birth weights of offspring of 62 MZ and 100 DZ smoking-discordant twin pairs were studied. Offspring of smoking MZ twins weighed 127 g less than birth order matched offspring of the non-smoking co-twins. This finding is additional evidence that smoking is a direct cause of reduced birth weight in offspring.

Birth Weight↗