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Biomedical subjects

R J Gardner

Publications and source records attributed to R J Gardner.

At least 19 recordsLinked to original sources
PubMed1992

Linkage of an important gene locus for tuberous sclerosis to a chromosome 16 marker for polycystic kidney disease.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder of unknown aetiology that affects numerous body systems including skin, brain and kidneys. Some TSC has been linked to chromosome 9, additional TSC genes on chromosomes 11 and 12 have been proposed, but the majority of TSC families remain unlinked. Using TSC families in which data had excluded linkage to chromosome 9, we failed to detect linkage with loci on chromosomes 11, 12 and others. One marker examined was D16S283, the closest locus on the proximal side of the polycystic kidney disease type 1 (PKD1) gene. Linkage between TSC and D16S283 demonstrated a lod score of 9.50 at theta = 0.02 with one family independently presenting a lod score of 4.44 at theta = 0.05. These data reveal an important TSC locus near the region of PKD1 on chromosome 16p13.

Alleles↗
PubMed1992

Experience with direct molecular diagnosis of fragile X.

The utility of the pfxa3 probe for direct molecular diagnosis of the fragile X (FRAXA) has been established. This probe detects amplification of an unstable DNA element consisting of variable length CCG repeats. The size of the amplified fragment is correlated with phenotype and was determined using PstI digested DNA in family members. In 35 families with the fragile X, there was correspondence in 183 cases between the presence of an amplified unstable element and the presence of the fragile X chromosome independently determined by cytogenetics, position in the pedigree, or linked DNA markers flanking the fragile X. There was also correspondence in 124 cases between the presence of the normal 1.0 kb PstI fragment and absence of the fragile X chromosome independently determined by linked flanking markers. Six additional families considered to be isolated cases of 'fragile X' had been diagnosed before recognition of FRAXD. The pfxa3 probe confirmed the cytogenetic diagnosis in three families, the other three being rediagnosed as non-fragile X. A further two families had consistent expression of a different folate sensitive fragile site, FRAXE, close to FRAXA but not associated with fragile X syndrome and not detectable with the pfxa3 probe. Subsequent referrals were received from additional family members or from members of new families for whom carrier status had not been predetermined by linked markers. Direct pfxa3 diagnosis for the 135 females within these 222 additional cases was confirmed by dosage analysis with the control probe pS8.(ABSTRACT TRUNCATED AT 250 WORDS)

Artifacts↗
PubMed1992

A small one-band paracentric inversion inv (4) (p15.3p16.3).

A neonate with aniridia was found to have a one band paracentric inversion of the short arm of chromosome 4. This was initially difficult to interpret on high resolution banding. The inversion was present in three generations of the family.

Aniridia↗
PubMed1991

Development of pragmatic exposure-control concentrations based on packaging regulation risk phrases.

This paper relates United Kingdom and other national Occupational Exposure Limits (OELs) for volatile organic substances to the Risk Phrases (RPs) which they are assigned under EEC Classification, Packaging and Labelling Directives. The OELs for organic volatiles assigned RP 20 ('harmful by inhalation'), RP 23 ('toxic by inhalation') and RP 26 ('very toxic by inhalation') fitted better to the cumulative log-normal distribution than to the cumulative normal distribution and the means for RPs 23 and 26 were not significantly different. The means for RP 20 and RP 23/26 were 100 mg m-3 (or 25 ppm) and 5 mg m-3 (or 1 ppm), respectively. In the absence of any relevant, specific information, it is suggested that these values may be useful as guidelines for pragmatic exposure-control concentrations (PECCs) for the control of exposure by inhalation in workplaces handling substances labelled with these RPs.

Environmental Exposure↗
PubMed1991

Inhalation anaesthetics--exposure and control during veterinary surgery.

Results are reported for air sampling surveys carried out by the Health and Safety Executive (HSE) in 14 veterinary surgeries. For all personnel the geometric mean (GM) time-weighted average (TWA) exposures to halothane and nitrous oxide over the working period were 2.6 ppm (range: less than 0.5 119 ppm) and 100 ppm (range: 14-1700 ppm), respectively. Since surgery rarely lasted for more than 4 h the corresponding GMs for 8-h TWAs were lower, being 1.3 ppm (range: less than 0.5-34 ppm) for halothane and 34 ppm (range: 5-530 ppm) for nitrous oxide. The GM exposures of veterinarians and nurses were very similar. The size of the practice and the use of scavenging were significant factors in determining personal exposures to inhalation anaesthetics: by comparison general ventilation had little effect. The results are compared with earlier data from human surgery, and previous studies of exposure to inhalation anaesthetics during veterinary surgery are briefly reviewed.

Anesthesia, Inhalation↗
PubMed1991

The phenotype in placental trisomy 7.

Trisomy 7, in mosaic state, was identified at chorionic villus sampling. The pregnancy was closely followed, and proceeded uneventfully. Mosaic trisomy 7 was confirmed in the term placenta, the organ having no structural abnormalities; the karyotype of the phenotypically normal baby was 46,XY. Trisomy 7, mosaic or nonmosaic, detected at chorionic villus sampling in an ultrasonographically normal pregnancy, appears typically to be associated with a normal fetal karyotype, and placental growth, structure, and function are not discernibly compromised.

Adult↗
PubMed1991

Linkage studies in tuberous sclerosis. Chromosome 9?, 11?, or maybe 14!

Published reports show linkage of tuberous sclerosis (TSC) to either chromosome 9 in some families or chromosome 11 in other families. We studied 243 individuals (82 with TSC) from 16 multigenerational TSC families. The diagnosis of TSC conformed to the criteria of Gomez. Penetrance was estimated at 0.90. DNA markers were analyzed using Southern blotting, probe hybridization, autoradiography, and genetic linkage analysis. Two-point lod scores for TSC were calculated for 43 genetic markers distributed over 11 chromosomes. Tests for homogeneity rejected the null hypothesis of homogeneity. Linkage to TSC was excluded (z less than or equal to -2, theta greater than or equal to 0.05) for 23 of these markers including 9q34 and 11q markers. One family gave z(theta max) = 1.8, theta max = 0.001 with ABO (on 9q34), and two other families attained lod scores greater than 1 for 9q34-region markers. The lod score for TSC versus chromosome 14 marker pAW101 (D14S1) was z(theta max) = 1.98, theta max = 0.15. A single large family has overall negative lod scores for markers localized to both chromosome 9 and chromosome 11. These data confirm genetic heterogeneity in TSC and suggest linkage of some families to 9q34. Furthermore, the data suggest that 14q may be an interesting area.

Chromosome Mapping↗
PubMed1990

Early prenatal diagnosis of genetic abnormality by chorion villus sampling.

We describe a series of 100 cases of prenatal genetic diagnosis using the technique of chorion villus sampling. The advantage of chorion villus sampling in terms of earlier diagnosis, and its disadvantage of a higher incidence of false results, compared with amniocentesis, are noted. The comparative risks for pregnancy loss are discussed.

Abortion, Spontaneous↗
PubMed1990

A DNA diagnostic service.

We describe the use of techniques of DNA analysis for the diagnosis of certain inherited diseases during life and in the prenatal period, and for the diagnosis of some infectious diseases. Most local and some national needs for predictive genetic testing have been met. The costs of establishing our service are presented and are compared with those of similar services recently established in the United Kingdom. In the 12 month period described, running costs were approximately $57,000 and salaries for the two scientific officers and the medical technologist required to run the service were $97,000. The prerequisites for the successful running of such a service are discussed.

Costs and Cost Analysis↗
PubMed1990

Syndrome of a craniofacial dysostosis, limb malformation, and omphalocele.

We describe an infant with a unique combination of a severe craniofacial dysostosis and a very distinctive facies, severe limb defects, a thoracic deformity, and an omphalocele as the major anomalies. We propose that this represents a "new" syndrome of multiple congenital abnormalities.

Abnormalities, Multiple↗
PubMed1990

Linkage of an autosomal dominant clefting syndrome (Van der Woude) to loci on chromosome Iq.

Van der Woude syndrome (VWS) is an autosomal dominant disorder in which affected individuals have one or more of the following manifestations: cleft lip, cleft palate, hypodontia, or paramedian lower-lip pits. VWS is a well-characterized example of a single-gene abnormality that disturbs normal craniofacial morphogenesis. As a first step in identifying genes involved in human development, we used a candidate-gene-and-region approach to look for a linkage to VWS. Six families with 3 or more generations of affected individuals were studied. Evidence for linkage (theta = 0.02, lod score = 9.09) was found between the renin (REN) gene on 1q and VWS. Other linked loci included CR1, D1S58, and D1S53. The genes for laminin B2 (LAMB2), a basement-membrane protein, and for decay-accelerating factor (DAF) were studied as possible candidate genes on 1q. Recombinants between VWS and both LAMB2 and DAF excluded these genes from a causal role in the etiology of VWS for the families studied in this report. Multipoint linkage analysis indicated that the VWS locus was flanked by REN and D1S65 at a lod score of 10.83. This tight linkage with renin and other nearby loci provides a first step in identifying the molecular abnormality underlying this disturbance of human development.

Chromosomes, Human, Pair 1↗