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Biomedical subjects

J M Connor

Publications and source records attributed to J M Connor.

At least 109 records · Page 6Linked to original sources
PubMed1991

Genotype prediction in the fragile X syndrome.

Fragile X positive, mentally retarded males have been shown to have an insertion or amplification of DNA sequences at, or close to, the site of expression of the fragile site. We show here the application of the detection of such changes to the diagnosis of affected males and female carriers and the identification of normal transmitting males. One fragile X negative male with the clinical features of the Martin-Bell syndrome also possesses an inserted/amplified DNA sequence. The implications of these results for screening for the fragile X syndrome are discussed.

Blotting, Southern↗
PubMed1991

Analysis of the origin of Turner's syndrome using polymorphic DNA probes.

Thirty-four families with a child or fetus with Turner's syndrome were studied using a series of polymorphic DNA probes. Analysis of the origin of the normal X chromosome was possible in all cases. In 16 families with 45,X (four fetuses and 12 livebirths), the observed X was maternal in each case, indicating a preferential loss of the paternal sex chromosome at, or before, conception. In the remaining 18 families with a variety of karyotypes, but especially in those where the child had an isochromosome of Xq or a ring X, there was again a strong tendency for the normal X to be maternal. Analysis of parental ages was performed with known origin of each abnormality, but no evidence for an increased or decreased parental age effect was detected.

Adult↗
PubMed1990

Patient care before and after termination of pregnancy for neural tube defects.

A retrospective study was designed to examine the perception of care in women who had experienced a second-trimester termination of pregnancy (TOP) for a neural tube defect. Women were identified over a 3-year period, 1983-1985. After appropriate consent, 166 women were visited at home between 4 weeks and 7 months post-TOP and interviewed by one experienced interviewer using a structured questionnaire with open and closed questions. The majority (137, 82 per cent) felt satisfied with the care received during screening, prenatal diagnosis, and during the TOP (126, 76 per cent). Patients were less satisfied (63, 38 per cent) with post-TOP care in hospital. On leaving hospital, the post-termination sequelae were mentioned to only 25 (15 per cent) patients, which left 135 (81 per cent) confused and bewildered by the post-partum reactions of their bodies, and by their strong emotions. After-care was perceived as unsatisfactory by 113 (68 per cent). One-quarter (42, 25 per cent) did not have, and were not invited for, a post-termination appointment and thus did not have an opportunity to ask questions or to discuss the fetus. Eighty-six (51.8 per cent) had no visit from any member of the primary health-care team, yet most would have appreciated such a visit. Suggestions for improved management are presented.

Abortion, Therapeutic↗
PubMed1990

Regional chromosomal assignment of the human mineralocorticoid receptor gene to 4q31.1.

The gene for human mineralocorticoid receptor (hMR), previously mapped to chromosome 4, has been further localized to 4q31.1 by in situ hybridization using a biotinylated 3.75 kb human cDNA clone encoding the primary amino acid sequence of hMR as a probe. Preliminary comparative mapping studies in orangutan (Pongo pygmaeus) suggest localization of the probe to the long arm of chromosome 3.

Animals↗
PubMed1990

Second-trimester placental biopsy for rapid fetal karyotyping.

Since January 1988 the technique of first-trimester chorionic villus sampling (placental biopsy) has been extended to include cases in the second trimester. To date, 40 procedures have been performed. The main indication for the late chorionic villus sampling was a low serum alpha-fetoprotein value in association with an increased risk for Down syndrome (n = 28), abnormal ultrasonographic finding (n = 7), and failed amniotic cell culture (n = 3). Successful karyotype results were achieved in all but two cases. Most results were obtained within 48 hours with direct cytogenetic techniques. No cases of mosaicism were found. The highest yield of abnormal karyotypes was obtained from the cases with abnormal ultrasonographic findings (one trisomy 21, two 45,X). One case of trisomy 21 was identified in the 28 cases of low serum alpha-fetoprotein. No spontaneous losses have occurred. The technique is easy to learn, does not differ from first-trimester procedures, and may have a lower complication rate than cordocentesis. The reporting of cases to the CVS Newsletter should help evaluate late chorionic villus sampling as another method for rapid fetal karyotyping.

Adult↗
PubMed1990

Analysis of Scottish Duchenne and Becker muscular dystrophy families with dystrophin cDNA probes.

One hundred and thirty-two Scottish families, representing the majority of currently known cases in this country with at least one living subject affected by DMD (110) or BMD (22), were studied with a series of cDNA probes excluding the 3' region of the gene (probes 10-14). Using mainly HindIII digested DNA from affected males, 89 patients showed deletions which ranged from 1 to 32 HindIII fragments in size. Two patients were also detected with exon duplications. Abnormalities were found to be particularly concentrated in the area of probe cDNA 8, with 56 patients being deleted for at least one of the fragments detected by this probe. A second smaller concentration of deletions was found with probe 1-2a which showed 16 deletions and two duplications. The endpoints of cDNA deletions or duplications were determined with a maximum variability of one HindIII fragment in 83 patients, while the remaining eight patients had a single deletion endpoint defined. The deletions found in two of our patients appear to conflict with the previously stated exon order at the 5' end of the gene. Although no specific deletion patterns were apparent for DMD, the deletions found in 13 of the BMD patients all included the most proximal (10 kb) fragment detected by probe 8.

Adolescent↗
PubMed1990

Genetic heterogeneity in tuberous sclerosis: phenotypic correlations.

There is increasing evidence for genetic heterogeneity in tuberous sclerosis (TSC) on the basis of linkage analysis in affected kindreds. We have performed a detailed assessment of an affected South African family in which there is no evidence of linkage to chromosome 9 markers. The affected persons have atypical clinical features, namely prominent nuchal skin tags, a confetti pattern of hypopigmentation of the skin of the lower legs, and absence of ungual fibromata. Further investigation of these unusual phenotypic features is warranted in order to determine whether these lesions are consistently present in families in whom the gene for TSC is not on 9q34. We conclude that confetti depigmentation and nuchal skin tags may be clinical pointers to an alternative locus for TSC.

Female↗
PubMed1989

Detection of a 15q deletion in a child with Angelman syndrome by cytogenetic analysis and flow cytometry.

A proximal 15q deletion, del(15) (q11:q13), was detected in a child with Angelman syndrome by cytogenetic analysis of peripheral lymphocytes. The chromosomes of both parents appeared normal. Flow karyotype analysis carried out on lymphoblastoid cell lines derived from the child and her parents confirmed the presence of a de novo 15 deletion. The estimated size of the deleted segment ranged from 6.1-9.5% of chromosome 15 (approximately 6-9.3 million base pairs). The parental origin of the deleted chromosome could not be resolved by flow cytometry, but cytogenetic evidence suggested that it was derived from the smaller chromosome 15 homologue in the mother.

Abnormalities, Multiple↗
PubMed1989

Detection of an unbalanced translocation (4;14) in a mildly retarded father and son by flow cytometry.

A child with impaired intelligence, minor dysmorphisms, obesity and genital hypoplasia was found to have an apparently balanced translocation, 46,XY,t(4;14)(q12;q13), following cytogenetic analysis. The same rearrangement was also detected in the child's father, who had similar phenotypic abnormalities to his son. Detailed study of flow karyotypes produced from lymphoblastoid cell lines established that in both patients the translocation was in fact unbalanced with approximately 11 million base pairs of DNA (corresponding to about 6.0% of chromosome 4 or 11.0% of chromosome 14) being lost.

Abnormalities, Multiple↗
PubMed1989

Isolation of chromosome-21-specific DNA probes and their use in the analysis of nondisjunction in Down syndrome.

Thirteen single-copy, chromosome-21-specific DNA probes were isolated from a recombinant library made from flow-sorted chromosome 21 DNA and regionally mapped using a panel of somatic cell hybrids. Five probes mapped in the 21q21-q22.1 region, six to the 21q22.1-qter region, and one to each of the regions 21q22.1-q22.2 and 21q22.3. Two of these probes, one of which maps in the critical region for Down syndrome, have recently been shown to be expressed at high levels in Down syndrome brain tissue (Stefani et al. 1988). Following preliminary screening for restriction fragment length polymorphisms (RFLPs), five polymorphisms were discovered with four of the chromosome 21 DNA probes. A frequent MspI polymorphism detected by one of the probes was used in conjunction with four previously described polymorphic chromosome 21 probes to analyse the origin of nondisjunction in 33 families with a child or fetus with trisomy 21. The parental origin of the additional chromosome 21 was determined in 12 cases: in 9 (75%) of these it was derived from the mother and in the other 3 cases (25%) it was of paternal origin. Cytogenetic analysis of Q-banding heteromorphisms was informative in three of five families tested, and in each case the RFLP results were confirmed. The meiotic stage of nondisjunction was defined with confidence in five families, the results being obtained with pericentromeric RFLP or cytogenetic markers. Recombination between two nondisjoined chromosomes was demonstrated in one family and is consistent with the view that a lack of recombination between chromosome 21 homologues or failure of their conjunction is not the invariable cause of trisomy 21.

Chromosome Banding↗
PubMed1989

Chromosomal assignment of a glutamic acid transfer RNA (tRNAGlu) gene to 1p36.

A gene for tRNAGlu has been assigned to human chromosome 1p36 by in situ hybridisation using a [3H]-labelled or biotinylated 2.4-kb (human) DNA fragment containing a tRNAGlu gene as a probe. With the biotinylated DNA probe a secondary statistically significant site of hybridisation was observed at 1q21-22 which might represent a pseudogene or related sequence. In fibroblasts from gorilla (Gorilla gorilla) using biotin labelling, a single site of hybridisation occurred at 1qter which provides further support for homology of 1q in the higher apes and human 1p.

Animals↗
PubMed1989

Genetic aspects of prenatal diagnosis.

With improved control of environmental agents, genetic conditions are now a major cause of residual handicap and mortality in all age groups. Primary prevention of this diverse group of over 5000 distinct disorders is not yet possible and effective therapy is, as yet, available for very few. Hence, the present emphasis on prevention is directed towards the identification and testing of pregnancies at risk in order to allow the option of early selective termination of pregnancy. Although over 400 distinct conditions have already been successfully prenatally diagnosed, the identification of at-risk pregnancies on the basis of a positive family history alone can identify only a minority of affected pregnancies. In contrast, genetic screening during (or before) pregnancy offers a real prospect for detection of a majority of affected pregnancies and hence for reducing the birth frequency of serious genetic conditions. This is exemplified by the impact of the maternal serum alpha-fetoprotein screening programme for neural tube defects and is under active development for autosomal aneuploidies and certain other major congenital malformations. These screening programmes will result in a reduced frequency of mental and physical handicap in the community but their implementation will require a comprehensive team approach with supraregional (or national) funding and co-ordination.

Abortion, Eugenic↗