Search PubMed⌕ Search

Biomedical subjects

D Curtis

Publications and source records attributed to D Curtis.

At least 163 records · Page 9Linked to original sources
PubMed1991

Specific diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in dried blood spots by a polymerase chain reaction (PCR) assay detecting a point-mutation (G985) in the MCAD gene.

The discovery of a point-mutation, adenine-to-guanine, at position 985 in the gene coding for MCAD (G985), gave the basis for an easy and specific polymerase chain reaction test. We tested the specificity of such a PCR based assay and detected correctly G985 and A985 in sequence verified cDNA clones. We showed that the G985 mutation is present in genomic DNA from 48 of 50 patients with confirmed MCAD deficiency, originating from various European countries, Australia and the USA. On the basis of this high frequency of the G985 mutation among patients, we improved and optimized the assay with respect to reliability and convenience for routine diagnostic and screening purposes. As little as 2 microliters blood from filter-paper blood-spots (Guthrie spots) is sufficient for the test.

Acyl-CoA Dehydrogenase↗
PubMed1991

The most common mutation causing medium-chain acyl-CoA dehydrogenase deficiency is strongly associated with a particular haplotype in the region of the gene.

RFLP haplotypes in the region containing the medium-chain acyl-CoA dehydrogenase (MCAD) gene on chromosome 1 have been determined in patients with MCAD deficiency. The RFLPs were detected after digestion of patient DNA with the enzymes BanII. PstI and TaqI and with an MCAD cDNA-clone as a probe. Of 32 disease-causing alleles studied, 31 possessed the previously published A----G point-mutation at position 985 of the cDNA. This mutation has been shown to result in inactivity of the MCAD enzyme. In at least 30 of the 31 alleles carrying this G985 mutation a specific RFLP haplotype was present. In contrast, the same haplotype was present in only 23% of normal alleles (P less than or equal to 3.4 x 10(-18)). These findings are consistent with the existence of a pronounced founder effect, possibly combined with biological and/or sampling selection.

Acyl-CoA Dehydrogenase↗
PubMed1991

A cosmid clone for the 5HT1A receptor (HTR1A) reveals a TaqI RFLP that shows tight linkage to dna loci D5S6, D5S39, and D5S76.

A human neuroreceptor clone (G21), which was isolated by cross-hybridization with the human clone for the beta 2-adrenergic receptor, has recently been shown to encode the gene for the 5HT1A receptor (HTR1A) subtype. In situ hybridization to human metaphase chromosomes mapped the G21 sequence to chromosome 5 at bands 5q11.2-q13. The clone G21 recognizes a SacI RFLP with low heterozygosity (0.13). To increase the informativeness of the HTR1A locus we have isolated two new cosmid clones containing the receptor gene. No polymorphic microsatellites were present in the cosmids. However, one cosmid revealed a new TaqI RFLP that showed tight linkage to new highly polymorphic microsatellites for the loci D5S76, D5S39, and D5S6 in seven British and Icelandic reference pedigrees (maximum LOD of 13.2 with D5S76).

Chromosome Mapping↗
PubMed1991

Genetic counselling for myotonic dystrophy: a comparison of lens examination and DNA linkage studies.

Genetic counselling in presymptomatic individuals with a family history of myotonic dystrophy (DM) is problematic. A genetic test to identify the presymptomatic carrier of the gene for DM would therefore be advantageous. We report studies comparing ophthalmic examination with a genetic test based on DNA linkage studies in nine DM families. The genetic test involved the use of five probes from four loci linked to the DM locus. Some discrepancies between ophthalmic and genetic tests were observed. Genetic counselling following prediction of genetic status was possible for 18 out of 20 patients from seven out of nine families.

Adolescent↗
PubMed1991

Gene conversion in Drosophila and the effects of the meiotic mutants mei-9 and mei-218.

Simple meiotic gene conversion tracts produced in wild-type females were compared with those from two meiotic mutants, mei-9 and mei-218. The positions and lengths of conversion tracts were determined by denaturing gradient gels and DNA sequencing. Conversion tracts in wild type averaged 885 base pairs in length, were continuous, and displayed no obvious hot spots of initiation. Some unusual conversion events were found in the mei-218 and mei-9 samples, although most events were indistinguishable from wild-type tracts in their length and continuity.

Animals↗
PubMed1991

Recovery from general anesthesia.

The pattern of recovery from anesthesia is ordinarily quite predictable. Using a limited number of drugs to provide anesthesia further improves predictability; it is more difficult to assign a cause for delayed emergence when multiple agents have been administered. We believe the recovery period is often more difficult to manage safely than induction and maintenance of anesthesia. During this phase, the effects of surgical trauma are superimposed on the patient's preexisting disease state, the anesthetic level is changing rapidly, respiratory function has not returned to normal, and circulatory reflexes may not have been regained. Because the patient is being moved from the operating room and care of the patient is being transferred from one person or team to others, vigilance and treatment may also be impaired. It is a period of care that warrants further study.

Anesthesia Recovery Period↗
PubMed1991

Psychological deficit from excessive alcohol consumption: evidence from a co-twin control study.

Twenty-five pairs of monozygotic twins discordant for either the alcohol dependence syndrome or heavy drinking were studied to determine the adverse cognitive effects of alcohol. The twins and their co-twins were well-matched for premorbid history and personality but twins with high alcohol consumption performed significantly less well overall on cognitive testing than their co-twins. Impaired performance in parts of the following tests was found: visual spatial ability, visual spatial recognition, Mill Hill vocabulary, Bexley Maudsley category sorting, tactual performance. The number of years of problem drinking correlated with inferior scores on subtests of the tactual performance test. This study provides further evidence that alcohol abuse produces long-term cognitive sequelae which may not be grossly evident in clinical practice, and which may occur even at relatively low levels of intake.

Alcohol Amnestic Disorder↗
PubMed1991

Piebaldism: an autonomous autosomal dominant entity.

Piebaldism is a disorder in which the major clinical features are patchy hypopigmentation of the skin and a white forelock. The manifestations of piebaldism overlap with those of other genodermatoses, in particular the Waardenburg syndrome, and it is uncertain whether piebaldism is a distinct entity. We have documented a family in which seven affected members in three generations have gross piebaldism without any additional stigmata. The intrafamilial phenotypic consistency is suggestive that this autosomal dominant disorder has independent syndromic status. Linkage studies using conventional gene markers failed to identity the locus of the faulty gene.

Adolescent↗
PubMed1991

Heterogeneity for mutations in medium chain acyl-CoA dehydrogenase deficiency in the UK population.

MCAD is the commonest inherited disorder of fatty acid oxidation. We have sought for and studied 21 affected children from 18 families within the UK. In 14 families the children are homozygous for the G985 mutation. In three families the children are compound heterozygotes for G985 and thus carry another and unknown mutation. In one family the child does not carry the G985 mutation on either allele. The carrier incidence of the G985 mutation is 1 in 68, which suggests that the natural history of MCAD deficiency deserves further study.

Acyl-CoA Dehydrogenases↗
PubMed1991

Using a dummy quantitative variable to deal with multiple affection categories in genetic linkage analysis.

Some diseases which have a genetic contribution to aetiology do not demonstrate a clear correspondence between genotype and phenotype. A variety of different clinical syndromes may be thought to reflect the action of a gene, but the probability of affection conditional on genotype may vary between these different diagnostic categories. The normal approach of repeating linkage analyses several times using different diagnoses to define individuals as affected loses power in two ways: multiple testing must be allowed for, and the distinction between more and less extreme forms of affection is lost. It is shown that for fully dominant or recessive autosomal diseases it is straightforward to assign a quantitative value to each diagnostic category to obtain the desired ratio of the likelihoods of affection conditional on the three possible genotypes. The increased power provided by using this quantitative value in linkage analysis is demonstrated by application to simulated pedigrees containing cases of bipolar and unipolar affective disorder.

Bipolar Disorder↗
PubMed1991

Hearing impairment and pigmentary disturbance.

Hearing impairment is a variable manifestation of several heritable conditions in which pigmentation of the skin or eyes is abnormal. Some of these disorders are well recognized although uncommon, while others are virtually private syndromes. Practical issues concerning the major conditions of this type are reviewed in this article on a basis of a survey of 4452 profoundly deaf children attending special schools in Southern Africa, together with investigations in affected families. The Waardenburg syndrome (WS), which is the most common deafness-depigmentation disorder, was present in 121 (2.7%) of the 4452 deaf scholars. Further studies in 7 multigeneration affected families confirmed phenotypic variability and indicated a need for internationally agreed diagnostic criteria. In 4 Cape Town families of mixed ancestry the WS-I gene was linked to the 2q37 locus, but in another large kindred no linkage could be demonstrated. Nonallelic heterogeneity is possible. There is uncertainty concerning possible interrelationship between WS and piebaldism. The phenotypic consistency of a South African family in which 7 persons in 3 generations had gross piebaldism in the absence of disturbance of hearing or involvement of the eyes and periorbital structures is suggestive that this disorder and WS are separate entities. Molecular investigations indicate that the gene for piebaldism in this kindred is not situated at the WS-I locus 2q37. Deafness and hyperpigmentation are present in neurofibromatosis type II (acoustic neuromata) and the multiple lentigines syndrome, while retinal pigmentation is a feature of the Usher syndrome. This latter entity is apparently much less common in Southern Africa than in other parts of the world.

Albinism↗