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Biomedical subjects

D Curtis

Publications and source records attributed to D Curtis.

At least 145 records · Page 8Linked to original sources
PubMed1993

Topics and signs: defensive control of emotional expression.

This single-case study examined frank disclosure of important topics in a brief exploratory psychotherapy, including topics closely related to a recent, unintegrated stressor life event. Quantitative measures of emotion and control variables showed heightened levels of both emotionally and defensive control during discourse on the topic of the stressor event. In future studies, such measures of verbal and nonverbal signs of emotional expression and defensive control might be used to identify topics in an unresolved state.

Adjustment Disorders↗
PubMed1993

Loss of heterozygosity of the thyroid hormone receptor B in posterior uveal melanoma.

Cytogenetic investigations of posterior uveal melanomas have identified non-random changes of chromosomes 3, 6, and 8. Monosomy of chromosome 3 with additional copies of 8q occur principally in the subgroup of uveal melanomas arising from the ciliary body. To determine whether ciliary body and choroidal melanomas maintain submicroscopic differences in their genetic aetiology, studies of the loss of heterozygosity (LOH) of THRB (ERBA beta) on 3p were undertaken. DNA from the blood and tumours of 19 patients with uveal melanoma were analysed for LOH of two restriction fragment length polymorphisms (RFLP). Approximately 60% of the uveal melanomas demonstrated allelic loss of THRB. Although the majority of tumours with allelic loss originated wholly, or in part, from the ciliary body, choroidal melanomas also demonstrated allelic loss of THRB. These results suggest that deletions of chromosome 3 occur in the absence of visible cytogenetic changes and may imply that alterations of chromosome 3 are integral to the tumourigenesis of both sets of uveal melanomas.

Choroid Neoplasms↗
PubMed1993

Segregation and linkage analysis in five manic depression pedigrees excludes the 5HT1a receptor gene (HTR1A).

Five kindreds selected through probands attending an Icelandic hospital were recruited for linkage studies of manic depression. The rates of affection were equal for males and females and the age of onset appeared to be predominantly in early adult life, since prevalence did not rise appreciably with age. A complex segregation analysis was performed using the computer program POINTER to obtain maximum likelihood estimates of the contributions to liability from multifactorial transmission and a single major locus. Likelihood ratios between models supported a role for a single major locus which was dominant and had moderately high penetrance with, in the case of unipolar illness, additional multifactorial transmission. The best-fitting parameters were used to devise a transmission model for linkage analysis. Three markers on chromosome 5 were studied, at D5S76, D5S6 and D5S39. Strongly negative lod scores were obtained which were less than -2 over a distance of 40 cM, which included the region to which the gene for the 5HT1a receptor has been mapped.

Bipolar Disorder↗
PubMed1993

Linkage analysis of Norrie disease with an X-chromosomal ornithine aminotransferase locus.

Norrie disease is a rare disease of newborn males caused by prenatal or perinatal retinal detachment, which may be associated with mental retardation, psychosis, and/or hearing loss. DXS7 (L1.28) and MAO A and B loci have been linked to the ND locus on the short arm of the X chromosome. Sequences homologous to OAT also have been mapped to the short arm of the X chromosome. We performed linkage analyses between the ND locus and one of the OAT-like clusters of sequences on the X chromosome (OATL1), using a ScaI RFLP in a ND family, and increased the previously calculated lod score (z) to over 3 (3.38; theta = 0.05). Similarly, we calculated a lod score of 4.06 (theta = 0.01) between the OATL1 and DXS7 loci. Alone, the OATL1 ScaI RFLP system is expected to be informative in 48% of females. If this system were used in combination with the DXS7 TaqI polymorphism, 71% of females would be informative for at least one of the markers and 21% would be informative for both. Because the OATL1 ScaI RFLP is a relatively common polymorphism, this system should be useful for the identification of ND carriers and affected male fetuses and newborns.

DNA↗
PubMed1993

Genetic linkage analysis of manic depression in Iceland.

Genetic linkage analysis has been used to study five Icelandic pedigrees multiply affected with manic depression. Genetic markers were chosen from regions which had been implicated by other studies or to which candidate genes had been localized. The transmission model used was of a dominant gene with incomplete penetrance and allowing for a large number of phenocopies, especially for unipolar rather than bipolar cases. Multipoint analysis with linked markers enabled information to be gained from regions spanning large distances. Using this approach we have excluded regions of chromosome 11p, 11q, 8q, 5q, 9q and Xq. Candidate genes excluded include those for tyrosine hydroxylase, the dopamine type 2 receptor, proenkephalin, the 5HT1A receptor and dopamine beta hydroxylase. Nevertheless, we remain optimistic that this approach will eventually identify at least some of the genes predisposing to manic depression.

Algorithms↗
PubMed1993

[Cleft lip and palate in the Chilean population: association with BamH1 polymorphism of the transforming growth factor alpha (TGFA) gene].

In recent studies we have demonstrated that the model that better explains the genetic etiology of non syndromic cleft lip/palate (CL/P) in the Chilean population is one that postulates the existence of a major dominant autosomic locus with low penetrance, without discarding the possible influence of polygenes. Similar conclusions have been communicated by others authors in different populations. Thus, investigations have been initiated to seek possible associations between candidate genes and restriction length polymorphisms (RFLP's), specifically between Transforming Growth Factor Alpha (TGFA) gene RFLP's and CL/P, in caucasian populations. Results thus far obtained have been inconclusive. Therefore, the aim of this work was to study this association in the Chilean population, that is ethnically different. The gene and phenotype frequencies of the TGFA gene BamH1 polymorphism in CL/P probands (n = 21) and controls (n = 16) were determined. No significant differences were detected in the frequencies of the A1 and A2 alleles of the TGFA gene between probands and controls. These results do not support an association between the cleft palate phenotype and TGFA RFLP.

Autoradiography↗
PubMed1993

Linkage analysis of idiopathic generalized epilepsy (IGE) and marker loci on chromosome 6p in families of patients with juvenile myoclonic epilepsy: no evidence for an epilepsy locus in the HLA region.

Evidence for a locus (EJM1) in the HLA region of chromosome 6p predisposing to idiopathic generalized epilepsy (IGE) in the families of patients with juvenile myoclonic epilepsy (JME) has been obtained in two previous studies of separately ascertained groups of kindreds. Linkage analysis has been undertaken in a third set of 25 families including a patient with JME and at least one first-degree relative with IGE. Family members were typed for eight polymorphic loci on chromosome 6p: F13A, D6S89, D6S109, D6S105, D6S10, C4B, DQA1/A2, and TCTE1. Pairwise and multipoint linkage analysis was carried out assuming autosomal dominant and autosomal recessive inheritance and age-dependent high or low penetrance. No significant evidence in favor of linkage was obtained at any locus. Multipoint linkage analysis generated significant exclusion data (lod score < -2.0) at HLA and for a region 10-30 cM telomeric to HLA, the extent of which varied with the level of penetrance assumed. These observations indicate that genetic heterogeneity exists within this epilepsy phenotype.

Adolescent↗
PubMed1992

Mutations in the medium chain acyl-CoA dehydrogenase (MCAD) gene.

Medium chain acyl-CoA dehydrogenase (MCAD) catalyzes the first reaction of the beta-oxidation cycle for 4-10-carbon fatty acids. MCAD deficiency is one of the most frequent inborn metabolic disorders in populations of northwestern European origin. In the compilation of data from a worldwide study of 172 unrelated patients each representing an independent pedigree, a total of 8 different mutations have been identified. Among them, a single prevalent mutation, 985A-->G, was found in 90% of 344 variant alleles. 985A-->G causes glutamate substitution for lysine-304 in the mature MCAD subunit, which causes impairment of tetramer assembly and instability of the protein. Three of 7 rarer mutations have been identified in a few unrelated patients, while the remaining 4 have each been found in only a single pedigree. In addition to tabulating the mutations, the acyl-CoA dehydrogenase gene family, the structure of the MCAD gene and the evolution of 985A-->G mutation are briefly discussed.

Acyl-CoA Dehydrogenase↗
PubMed1992

The ocular pathology of Norrie disease in a fetus of 11 weeks' gestational age.

The ocular pathology of Norrie disease was studied for the first time in a fetus of 11 weeks' gestation, following prenatal diagnosis using genetic markers for Norrie disease and elective abortion. The eyes were histologically normal, with no evidence of primary neuroectodermal maldevelopment of the retina, previously postulated to be the cause of the ocular changes. We believe that the retinal and other manifestations of Norrie disease are the result of a primary abnormality of vascular proliferation, probably in relation to persistent hyperplastic primary vitreous after approximately 14 weeks' gestation. We postulate that the ocular and otological effects of Norrie disease may be due to a genetically mediated abnormality of secretion of, or sensitivity to, angiogenic growth factors at endodermal-neuroectodermal interfaces during fetal and postnatal development.

Abortion, Legal↗
PubMed1992

Autosomal dominant gene transmission in a large kindred with Gilles de la Tourette syndrome.

A multiplex kindred ascertained through a single proband with GTS has been systematically investigated with standardised diagnostic instruments for other cases of GTS and related disorders. Complex segregation analysis supported the hypothesis that a single major gene inherited in autosomal dominant fashion but with incomplete penetrance contributed most of the variance in the liability to develop GTS and related disorders. This result is consistent with previous segregation analyses which have employed different methods of ascertainment, and tends to confirm that a proportion of GTS is due to a dominant gene and is suitable for investigation with genetic markers for linkage analysis.

Causality↗
PubMed1992

Mutations of the KIT (mast/stem cell growth factor receptor) proto-oncogene account for a continuous range of phenotypes in human piebaldism.

Piebaldism is a rare autosomal dominant disorder of pigmentation, characterized by congenital patches of white skin and hair from which melanocytes are absent. We have previously shown that piebaldism can result from missense and frameshift mutations of the KIT proto-oncogene, which encodes the cellular receptor tyrosine kinase for the mast/stem cell growth factor. Here, we report two novel KIT mutations associated with human piebaldism. A proximal frameshift is associated with a mild piebald phenotype, and a splice-junction mutation is associated with a highly variable piebald phenotype. We discuss the apparent relationship between the predicted impact of specific KIT mutations on total KIT-dependent signal transduction and the severity of the resultant piebald phenotypes.

Amino Acid Sequence↗