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J E Spence

Publications and source records attributed to J E Spence.

At least 37 records · Page 2Linked to original sources
PubMed1991

Tracheomalacia in Hallermann-Streiff syndrome.

We report on a white boy with Hallermann-Streiff syndrome (HSS) who also had tracheomalacia. Chronic respiratory insufficiency led to biventricular failure and death at age 6 months. There have been no previously reported cases of Hallermann-Streiff syndrome with documented tracheomalacia. However, there may be cases in which tracheomalacia may have been present, but not diagnosed. The literature contains 6 HSS cases with severe respiratory symptoms. Tracheomalacia should be considered in a patient with HSS who presents with an unusual cry, stridor, choking, or apnea. With the availability of surgery and supportive treatment, early diagnosis of tracheomalacia in these patients may prevent death and secondary neurologic insult from acute hypoxia.

Cartilage Diseases↗
PubMed1991

Monozygotic twins discordant for Ullrich-Turner syndrome.

We describe 9-year-old twin girls who were thought to be monozygotic but who differed greatly in physical appearance and growth pattern. One twin had Ullrich-Turner syndrome (UTS), 45,X/46,XX mosaicism in peripheral blood, and only 45,X cells in skin fibroblasts. The phenotypically normal twin also had 45,X/46,XX mosaicism in blood but only 46,XX cells in cultured fibroblasts. Analysis of DNA marker patterns in blood lymphocytes and in skin fibroblasts confirmed monozygosity with a probability of 99.97%. This case is compared with other reported cases of discordance for UTS in twins. It is concluded that essentially all of the differences between the two twins can be explained by loss of an X chromosome early in embryogenesis with complete separation of 45,X and 46,XX cell lineages at the time of the twinning event. The presence of mosaicism in the peripheral blood of both twins is presumably due to anastomoses between the placentae resulting in a mixture of the two cell populations in the hematopoietic tissue.

Child↗
PubMed1991

A molecular genetic approach to the identification of isochromosomes of chromosome 21.

The largest class of de novo chromosomal rearrangements in Down syndrome are rea(21q21q). Classically, these rearrangements have been termed Robertsonian translocations, implying an attachment of two different chromosome 21 homologues. Additionally, a Robertsonian translocation between two chromosomes 21 cannot be distinguished from an isochromosome composed of genetically identical arms by cytogenetic analyses. Therefore, we have used molecular techniques to differentiate between true Robertsonian translocations and isochromosomes. Samples were obtained from 12 probands, ascertained for de novo rearrangements between homologous chromosomes 21 [11 rea(21q21q) and 1 rea (21;21)(q22;q22)], their parents (n = 24) and available siblings (n = 7). The parental origins of the de novo rearrangements were assigned using molecular and cytogenetic analyses. Although not statistically significant, there was a two-fold increase in the number of paternally derived de novo rearrangements (n = 8) as compared with maternally derived rearrangements (n = 4). To distinguish between rob(21q21q) and i(21q), we used restriction fragment length polymorphisms (RFLPs) spanning the length of chromosome 21. Using all informative and partially informative RFLPs, we used the method of maximum likelihood to assign the most likely rearrangement definition (i or rob) and parental origin in each family. The maximum likelihood estimates indicated that all rearrangements tested (n = 8) were isochromosomes. C-banding revealed two centromeres in three cases indicating that a U-type exchange occurred between sister chromatids in these rearrangements. Our results suggest that the majority of de novo rea(21q21q) are isochromosomes derived from a single parental chromosome 21.

Cells, Cultured↗
PubMed1991

Innovations in human genetics education. Medical student elective in clinical genetics.

The fourth-year medical student elective in clinical genetics has been enhanced by the addition of a problem-solving project. The assignment requires students to pose and answer a practical question about a professionally relevant genetic problem. Exemplary questions and the details of the exercise are given. Six of 10 students choosing an elective in clinical genetics have undertaken the project. Their feedback suggests that the requirements of decision making, library research, discussion with consultants, and medical writing in a limited time period are beneficial additions to the standard elective.

Curriculum↗
PubMed1989

Endocervical Chlamydia trachomatis infection in Canadian adolescents.

The highest prevalence rate of sexually transmitted chlamydial infection is among adolescent girls. To determine the rate among predominantly asymptomatic girls who were seen at a pediatric gynecology unit and to identify those at high risk we screened 541 such patients from Jan. 1 to Dec. 31, 1986, by means of direct fluorescent antibody testing; 422 (78.0%) were asymptomatic. The most common reason for presentation was a request for contraceptive advice (the reason for 59.2% of the patients). Of the 446 patients (82.4%) who were sexually active 66 (14.7%) had evidence of chlamydial infection; none of the 93 sexually inactive patients were infected. Neisseria gonorrhoeae was isolated from eight (1.5%) of the patients. The risk factors that correlated with chlamydial infection were abnormal vaginal discharge, abdominopelvic pain and an abnormal Papanicolaou test result. Because of the high morbidity rate associated with genital chlamydial infection and the high prevalence rate among adolescent girls, most of whom are asymptomatic, all sexually active teenagers should be screened.

Adolescent↗
PubMed1989

Prenatal diagnosis and heterozygote detection by DNA analysis in ornithine transcarbamylase deficiency.

This report summarizes our experience with DNA analysis using a complementary DNA probe for ornithine transcarbamylase in 24 individuals or families with deficiency of this enzyme. In four cases, including three reported elsewhere, a Taql restriction site alteration directly detected the mutation. In 10 additional cases, only an affected male was available, and results of DNA analysis using the Taql enzyme were normal. In 10 cases, family studies were performed with the use of restriction fragment length polymorphisms. Prenatal diagnostic studies were performed for three informative pregnancies, and two affected male fetuses were identified. Analysis of two restriction fragment length polymorphisms, Mspla and BamHl, was informative in 14 of 19 (74%) known carrier females and in 21 of 35 (60%) females (the total number studied). One female previously predicted to be a noncarrier by protein-loading test was determined to be a carrier by analysis of restriction fragment length polymorphisms. The frequency of Taql site alterations was 4 of 24 families (17%). These data illustrate the importance of DNA analysis, pedigree analysis, and biochemical testing in families with ornithine transcarbamylase deficiency to detect carriers and establish the diagnosis prenatally.

Blotting, Southern↗
PubMed1989

The measurement of surface area of endometriotic implants by morphometric analysis.

There are numerous staging methods for the assessment and evaluation of endometriosis both before and after treatment. Present systems rely on subjective criteria that are prone to bias and error. This report describes an objective technique for the measurement of surface area of pelvic endometriotic implants that is both accurate and reproducible. Six patients with endometriosis underwent laparoscopy and were staged using the Revised American Fertility Society criteria; the lesions were photographed simultaneously. These patients were then treated with either danazol or Nafarelin acetate for 6 months before a second-look laparoscopy. Using coded photographic slides, implants were measured using computerized morphometric analysis. An accurate record of the number and surface area of the lesions was obtained before and after treatment. The mean surface area of individual lesions and the total visible disease per patient fell by 89 and 82%, respectively. The mean number of lesions per patient actually rose by 30% as a result of fragmentation into smaller plaques. These data suggest that morphometry may be more valuable in the assessment of endometriotic implants than are all previously described staging systems.

Endometriosis↗
PubMed1988

Characterization of point mutations in the same arginine codon in three unrelated patients with ornithine transcarbamylase deficiency.

Point mutations in the X-linked ornithine transcarbamylase (OTC) gene have been detected at the same Taq I restriction site in 3 of 24 unrelated probands with OTC deficiency. A de novo mutation could be traced in all three families to an individual in a prior generation, confirming independent recurrence. The DNA sequence in the region of the altered Taq I site was determined in the three probands. In two unrelated male probands with neonatal onset of severe OTC deficiency, a guanine (G) to adenine (A) mutation on the sense strand (antisense cytosine [C] to thymine [T]) was found, resulting in glutamine for arginine at amino acid 109 of the mature polypeptide. In the third case, where the proband was a symptomatic female, C to T (sense strand) transition converted residue 109 to a premature stop. These results support the observation that Taq I restriction sites, which contain an internal CG, are particularly susceptible to C to T transition mutation due to deamination of a methylated C in either the sense or antisense strand. The OTC gene seems especially sensitive to C to T transition mutation at arginine codon 109 because either a nonsense mutation or an extremely deleterious missense mutation will result.

Adult↗
PubMed1988

Uniparental disomy as a mechanism for human genetic disease.

A female with cystic fibrosis and short stature was investigated for molecular or cytogenetic abnormalities that might explain the combined phenotype. Analysis with polymorphic DNA markers indicated that the father did not contribute alleles to the propositus for markers near the CF locus or for centromeric markers on chromosome 7. High-resolution cytogenetic analysis was normal, and the result could not be explained on the basis of nonpaternity or a submicroscopic deletion. All of the data indicate that the propositus inherited two identical copies of maternal sequences for much or all of chromosome 7. The occurrence of uniparental disomy could be explained by models postulating postfertilization error, gamete complementation, monosomic conception with subsequent chromosome gain, or trisomic conception followed by chromosome loss. Uniparental disomy in an individual with a normal chromosome analysis is a novel mechanism for the occurrence of human genetic disease.

Adolescent↗
PubMed1988

Prenatal diagnosis of cystic fibrosis: microvillar enzymes and DNA analysis compared.

We have established reference ranges for three microvillar intestinal enzymes--alkaline phosphatase (EC 3.1.3.1), gamma-glutamyltransferase (EC 2.3.2.1), and leucine aminopeptidase (EC 3.4.1.1)--measured in amniotic fluid in a reference population of 1875 women presenting for routine amniocentesis. These data were derived for use in prenatal diagnostic studies in a population at risk (1:4) for cystic fibrosis. False-positive or indeterminate results were noted for fewer than 3.5% of all low-risk cases for each enzyme evaluated. Total alkaline phosphatase and its isoenzymes and leucine amino-peptidase and gamma-glutamyltransferase were measured in amniotic fluid sampled between the 15th and 19th weeks of gestation. Restriction fragment length polymorphism analysis of DNA was also performed when possible. In 52 cases examined for cystic fibrosis thus far, 46 were diagnosed on the basis of DNA analysis and (or) by sweat testing; for the other six cases, only abnormal enzyme results were obtained before termination of pregnancy. Predictions based on microvillar enzyme results were falsely negative in three cases. In only one case was there a discrepancy between enzyme results and DNA analysis. Diagnostic accuracy was highest during the 17th and 18th week of gestation. Preliminary results suggest the false-negative rate of this diagnostic strategy may be greater than or equal to 10%.

Alkaline Phosphatase↗
PubMed1987

Prenatal diagnosis of cystic fibrosis using linked DNA markers and microvillar intestinal enzyme analysis.

Prenatal diagnosis was performed for 47 pregnancies with 1 in 4 risk of cystic fibrosis, including 7 cases analyzed with linked DNA markers, 16 cases analyzed by microvillar intestinal enzyme testing, and 24 cases where both methods of testing were attempted. DNA was obtained by chorionic villus sampling in 10 cases and by amniocentesis in 21 cases, and diagnosis was based on analysis with the tightly linked DNA markers D7S8 and met. DNA analysis using these probes was fully informative in 74.4% of 90 couples with 1 in 4 risk. In 18 cases where both DNA results and microvillar intestinal enzyme data were diagnostic, there was agreement regarding the predicted status of the fetus. No adequate diagnosis was achieved in two cases where both diagnostic tests were attempted. Outcome is known for 24 pregnancies including 10 where DNA analysis was diagnostic, and no errors in diagnosis were detected. Prenatal diagnosis of cystic fibrosis using DNA markers is highly informative and accurate, but microvillar intestinal enzyme analysis remains a valuable part of a complete diagnostic program.

Alkaline Phosphatase↗
PubMed1987

Endometrial prostaglandins and menorrhagia: influence of a prostaglandin synthetase inhibitor in vivo.

Prostaglandin levels in the human endometrium were determined on day 2 of the menstrual cycle in eumenorrheic subjects and in patients with menorrhagia, dysmenorrhea, or both. Menorrhagic subjects had significantly higher levels of endometrial prostaglandins of the E and F series when compared with eumenorrheics. Prostaglandin E levels were markedly higher than prostaglandin F. In 10 menorrhagic subjects who completed a double-blind clinical study on the effectiveness of mefenamic acid in lowering menstrual blood loss, 9 exhibited statistically significant reduction in endometrial prostaglandin levels. A decrease in menstrual blood loss was also noted during mefenamic acid treatment in these patients. These findings are consistent with the concept that abnormally high uterine prostaglandin levels may be an important etiologic factor in menorrhagia and support the notion that one of the mechanisms of action of nonsteroidal anti-inflammatory agents in the treatment of this menstrual disorder is inhibition of endometrial prostaglandin production.

Adult↗
PubMed1986

Atypical presentation and neuropathological studies in 3-hydroxy-3-methylglutaryl-CoA lyase deficiency.

A 6 1/2-month-old male offspring of consanguineous Egyptian parents was first seen because of fever, somnolence, vomiting, right focal motor seizures, right hemiparesis, elevated transaminase levels, hyperammonemia, and acidosis. A computed tomographic scan of the head suggested swelling of the left cerebral hemisphere, and an electroencephalogram indicated left frontotemporal abnormalities, but brain biopsy demonstrated diffuse white matter spongiosis and gliosis. Subsequently, urine organic acid analysis and enzyme assays were diagnostic of 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency.

Brain↗
PubMed1986

Linkage of DNA markers to cystic fibrosis in 26 families.

Two DNA markers, the met oncogene and the anonymous probe, pJ3.11, previously reported to be tightly linked to cystic fibrosis (CF), were used for linkage analysis in 26 families with two or more individuals affected with CF. A new high frequency polymorphism was identified using BanI and the pmetD probe. The results of linkage analysis were as follows: between met and CF, lod score of 18.2 at theta of .009; between pJ3.11 and CF, lod score of 12.1 at theta of 0; and between met and pJ3.11, lod score of 16.7 at theta of 0. These data indicate that most or all of CF is due to an abnormality at a single locus and that the DNA markers are useful for prenatal diagnosis and heterozygote detection within affected families.

Cystic Fibrosis↗