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C M Gosden

Publications and source records attributed to C M Gosden.

At least 19 recordsLinked to original sources
PubMed2000

Chorion villus sampling versus amniocentesis for prenatal diagnosis.

BACKGROUND: Amniocentesis test results are usually available only after 18 weeks gestation. Chorion villus sampling (CVS) may be performed transabdominally or transvaginally, usually between 10 and 12 weeks gestation. OBJECTIVES: The objective of this review was to assess the safety and accuracy of chorion villus sampling compared to amniocentesis. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register. SELECTION CRITERIA: Randomised trials comparing first trimester chorion villus sampling and second trimester amniocentesis. DATA COLLECTION AND ANALYSIS: Trial quality was assessed. MAIN RESULTS: Three studies involving over 9000 women were included. The trials were generally of good quality. Compared to amniocentesis, chorion villus sampling was associated with more sampling and technical failures, and more false positive and false negative results. Pregnancy loss was more common after chorion villus sampling (odds ratio 1.33, 95% confidence interval 1.17 to 1.52). There is a suggestion (though not statistically significant) of an increase in stillbirths and neonatal deaths following chorion villus sampling. Maternal complications were uncommon. REVIEWER'S CONCLUSIONS: The increase in miscarriages after chorion villus sampling compared to amniocentesis appear to be procedure related. Second trimester amniocentesis appears to be safer than chorion villus sampling. The benefits of earlier diagnosis with chorion villus sampling must be set against the greater risk of pregnancy loss.

Chorionic Villi Sampling↗
PubMed1999

Ontogeny of interstitial cells of Cajal in the human intestine.

BACKGROUND/PURPOSE: Interstitial cells of Cajal (ICC) recently have been identified as intestinal pacemaker cells. Abnormalities in ICC are increasingly recognized in a number of neonatal disorders such as infantile hypertrophic pyloric stenosis, Hirschsprung's disease, and transient intestinal pseudo-obstruction. The aim of this study was to determine the fetal and postnatal differentiation and development of ICC in the human gastrointestinal tract to aid interpretation of pathological specimens. METHODS: Specimens of human gastrointestinal tract from (1) fetuses (9 to 17 weeks' gestation; n = 12), (2) premature and full-term neonates with non-gut motility-related disorders, (age 26 to 59 weeks' gestation; n = 13), and (3) children (age 4 months to 13 years; n = 7) were immunohistochemically stained with antibodies to c-kit(a marker for ICC) and protein gene product 9.5 (PGP9.5, a marker for neural tissue). RESULTS: (1) C-kit-positive ICC were present throughout the gut in all specimens including those from the earliest gestational ages. C-kit and PGP9.5 immunoreactivities were present in different cell populations. (2) The distribution of ICC varied with gestational age and with region of the gut. (3) Maturation of ICC networks continues postnatally in a region-specific manner. CONCLUSIONS: ICC are present from an early stage in human gut development. Interpretation of apparent abnormalities in ICC distribution as being of pathological significance should be tempered by the knowledge that ICC networks continue to develop postnatally and that ICC development varies throughout the gut.

Child↗
PubMed1998

The Knights of the Round Table hypothesis of tumour suppressor gene function--noble sacrifice or sexual dalliance: genes, including p53, BRCA1/2 and RB have evolved by horizontal and vertical transmission of mating factor genes and are involved in gametogenesis, implantation, development and tumourigenesis.

The genes involved in negative cell cycle regulation and familial tumour susceptibility including APC, BRCA, p53, RB, WT1 are unique and have no homologies with other genes. Our hypothesis suggests they originated from mating factor genes, which halted cell division in response to stress to generate genetic diversity by sexual mechanisms. Some have evolved principally by vertical transmission (mismatch repair), others by horizontal transmission via mobile elements, predominantly in oocytes. We demonstrate amplification in human extra-embryonic tissues in fetus and mother in implantation; in the developing fetus, differing tissue-specific patterns are seen, especially between testis and ovary. We suggest that the fetus is susceptible to maternal transmission of infections including CMV, malaria, trypanosomes, whose sequences occur within these genes. In head and neck cancers, we demonstrate specific patterns of loss or instability involving up to seven different TSG. We suggest mechanisms of tumourigenesis involve transposable elements and episome formation, leading to loss of negative cell cycle regulation and exit from G0.

Animals↗
PubMed1995

Identifying genes within microdissected genomic DNA: isolation of brain expressed genes from a translocation region associated with inherited mental illness.

An improved protocol has been developed for physical enrichment of cDNA sequences by hybridization to genomic DNA. When applied to microdissection recombinants derived from a translocation breakpoint region associated with inherited mental illness, a single cycle of the procedure permitted enriched cDNAs to be visualized directly by agarose gel electrophoresis. Hybridization screening of a library of clones derived from the enriched cDNAs, employing the genomic resource as a probe, led to the identification of six novel gene fragments. This general approach to the isolation of regionally encoded genes could be applied to any subchromosomal interval as a first step towards global transcription map construction.

Animals↗
PubMed1995

Partial hydatidiform mole and hypertension associated with a live fetus--variable presentation in two cases.

Partial hydatidiform mole associated with live births is a rare condition. There are not enough cases in the literature to allow the assessment of comprehensive risks to be made and upon which management policies can be based. Several clinical dilemmas arise following diagnosis of a viable pregnancy associated with molar tissue. We present two cases demonstrating the problems and suggest management based on outcome and a review of the literature.

Adult↗
PubMed1995

Direct microdissection and microcloning of a translocation breakpoint region, t(1;11)(q42.2;q21), associated with schizophrenia.

We describe the generation of large-fragment microclone libraries from the chromosomal breakpoint of a reciprocal balanced translocation linked to schizophrenia. The abnormality was visible under the phase-contrast microscope, allowing direct dissection from unstained, unbanded metaphases. Two separate microdissection experiments yielded 443 and 672 recombinants, respectively. Following complete EcoRI digestion, inserts with an average size of 0.3 kb (range, 0.2-3 kb) were obtained in the first experiment and 1.5 kb (range, 0.15-6.5 kb) in the second. FISH analysis of pooled clones "painted" back onto the derivative chromosome and assignment of microclones to somatic cell hybrids confirmed the fidelity of the method. Microdissection of chromosome regions identified by karyotype rearrangements in unstained, unbanded metaphases is a potentially powerful tool for positional cloning.

Base Sequence↗
PubMed1994

Prenatal diagnosis of fragile X syndrome: management of the male fetus with a premutation.

Direct detection of the fragile X mutation by DNA analysis has greatly simplified prenatal diagnosis of this disease. However, women carrying a fragile X premutation may pass their expanded trinucleotide repeat to sons without expansion to a full mutation. Such sons are predicted to be intellectually normal. In this situation, the accuracy with which the fetal status can be inferred from analysis of chorionic villus sample (CVS) DNA is unclear. We describe such a case, in which it was felt necessary to proceed to fetal blood sampling despite technically unambiguous DNA results from the CVS. The lack of prospective data means that this dilemma may be expected to recur over the next few years when performing prenatal diagnosis on fragile X premutation carriers.

Adult↗
PubMed1994

Parental origin of transcription from the human GNAS1 gene.

Variation in the phenotypic expression of Albright's hereditary osteodystrophy (AHO) determined by the parent of transmission, suggests that the human Gs alpha gene (GNAS1), in which mutations occur in AHO, may be under imprinted control. GNAS1 is also known to map to a chromosomal region (20q13.11) showing syntenic homology with the imprinted mouse region 2E1-2H3. To establish if GNAS1 is indeed imprinted, we have examined the parental origin of GNAS1 transcription in human fetal tissues. Of 75 fetuses genotyped, at gestational ages ranging from 6 to 13 weeks, 13 heterozygous for a FokI polymorphism in exon 5 of GNAS1 were identified whose mothers were homozygous for one or other allele. RNA from up to 10 different tissues from each fetus was analysed by RT-PCR. In all cases expression from both parental alleles was shown by FokI digestion of RT-PCR products and quantification of the resulting fragments. No tissue specific pattern of expression was discerned in these experiments. If genomic imprinting regulates the expression of the human GNAS1 gene, our data suggest that the effect must either be subtle and quantitative, or be confined to a small subset of specialised hormone responsive cells within the target tissues.

Alleles↗
PubMed1994

Genetic heterogeneity in X-linked hydrocephalus: linkage to markers within Xq27.3.

X-linked hydrocephalus is a well-defined disorder which accounts for > or = 7% of hydrocephalus in males. Pathologically, the condition is characterized by stenosis or obliteration of the aqueduct of Sylvius. Previous genetic linkage studies have suggested the likelihood of genetic homogeneity for this condition, with close linkage to the DXS52 and F8C markers in Xq28. We have investigated a family with typical X-linked aqueductal stenosis, in which no linkage to these markers was present. In this family, close linkage was established to the DXS548 and FRAXA loci in Xq27.3. Our findings demonstrate that X-linked aqueductal stenosis may result from mutations at two different loci on the X chromosome. Caution is indicated in using linkage for the prenatal diagnosis of X-linked hydrocephalus.

Cells, Cultured↗
PubMed1993

Fetal growth retardation: associated malformations and chromosomal abnormalities.

OBJECTIVE: Our objective was to determine the incidence and pattern of chromosomal abnormalities in fetal growth retardation. STUDY DESIGN: Blood karyotyping was performed in 458 fetuses referred to us for further assessment of growth retardation at 17 to 39 weeks' gestation. RESULTS: The fetal karyotype was normal in 369 and abnormal in 89 (19%) of the cases. The most common chromosomal defect in the group referred at < 26 weeks' gestation was triploidy; in those referred at > or = 26 weeks, it was trisomy 18. The incidence of fetal autosomal chromosome aberrations increased, whereas the incidence of triploidy did not change, with maternal age. Ninety-six percent of chromosomally abnormal fetuses had multisystem fetal defects that were characteristic of the different types of chromosomal abnormalities. Compared with those fetuses with a normal karyotype, the chromosomally abnormal group had a higher mean head circumference/abdominal circumference ratio, a higher incidence of normal or increased amniotic fluid volume, and normal waveforms from the uterine or umbilical arteries or both. CONCLUSION: The findings of the different types of chromosomal abnormalities and their ultrasonographically detectable phenotypic expression provide the background for prospective studies to determine the incidence of chromosomal abnormalities in unselected populations of small-for-gestational-age fetuses.

Abnormalities, Multiple↗
PubMed1993

De novo microdeletion on an inherited Robertsonian translocation chromosome: a cause for dysmorphism in the apparently balanced translocation carrier.

Robertsonian translocations are usually ascertained through abnormal children, making proposed phenotypic effects of apparently balanced translocations difficult to study in an unbiased way. From molecular genetic studies, though, some apparently balanced rearrangements are now known to be associated with phenotypic abnormalities resulting from uniparental disomy. Molecular explanations for other cases in which abnormality is seen in a balanced translocation carrier are being sought. In the present paper, an infant is described who has retarded growth, developmental delay, gross muscular hypotonia, slender habitus, frontal bossing, micrognathia, hooked nose, abundant wispy hair, and blue sclerae. Cytogenetically, she appeared to be a carrier of a balanced, paternally derived 14;21 Robertsonian translocation. Analysis of DNA polymorphisms showed that she had no paternal allele at the D14S13 locus (14q32). Study of additional DNA markers within 14q32 revealed that her previously undescribed phenotype results from an interstitial microdeletion within 14q32. Fluorescent in situ hybridization was used to show that this microdeletion had occurred de novo on the Robertsonian translocation chromosome. These observations may reactivate old suspicions of a causal association between Robertsonian translocations and de novo rearrangements in offspring; a systematic search for similar subcytogenetic rearrangements in other families, in which there are phenotypically abnormal children with apparently balanced translocations, may be fruitful. The clinical and molecular genetic data presented also define a new contiguous gene syndrome due to interstitial 14q32 deletion.

Abnormalities, Multiple↗
PubMed1992

Ultrasonographically detectable markers of fetal chromosomal abnormalities.

Screening for fetal chromosomal abnormalities on the basis of maternal age has not resulted in a substantial fall in the proportion of infants born with an abnormal karyotype. Most fetuses with major chromosomal abnormalities have defects that can be recognised on detailed ultrasonographic examination. Therefore, provided the cardinal signs of each chromosomal syndrome are recognised, it is possible that screening by ultrasound examination could have a greater impact. We karyotyped 2086 fetuses after ultrasonographic examination had revealed fetal malformations, growth retardation, or both. Chromosomal abnormalities were detected in 301 (14%) cases and were more common among fetuses with multisystem malformations (29%) than among those with isolated defects (2%). The commonest chromosomal abnormality was trisomy 18, followed by trisomy 21, triploidy, Turner's syndrome, unbalanced chromosomal rearrangements, and trisomy 13. Trisomy 18 was associated with strawberry-shaped head, choroid plexus cysts, facial cleft, micrognathia, heart defects, exomphalos, malformations of hands and feet, and growth retardation. In trisomy 21, the associated defects were subtle and included nuchal oedema, macroglossia, atrioventricular septal defects, mild hydronephrosis, clinodactyly, and sandal gap. The frequency of autosomal abnormalities increased with maternal age, but if fetal karyotyping had been restricted to mothers older than 35 years, large proportions of chromosomally abnormal fetuses would not have been diagnosed prenatally (64-97%). Our findings provide guidelines as to which defects to search for in screening studies for the detection of chromosomal abnormalities.

Adolescent↗
PubMed1992

Fetal nuchal oedema: associated malformations and chromosomal defects.

During an 8-year period, oedema in the dorsal cervical region that produces a characteristic tremor on ballotement of the fetal head (nuchal oedema) was observed in 145 (7%) of the 2,086 fetuses that underwent karyotyping in our unit because of fetal malformations and/or growth retardation. Nuchal oedema was distinguished from nuchal cystic hygromata and from hydrops foetalis. In 132 (91%) of the cases with nuchal oedema, there were other fetal malformations, and 53 (37%) fetuses had chromosomal abnormalities, mainly trisomy 21 but also other trisomies, deletions or translocations, triploidy and Turner syndrome. Furthermore, the chromosomally normal fetuses with nuchal oedema had a very poor prognosis because, in many cases, there was an underlying skeletal dysplasia, a genetic syndrome or cardiac defect.

Abnormalities, Multiple↗
PubMed1992

Strawberry-shaped skull in fetal trisomy 18.

During an 8-year period, a strawberry-shaped skull (flattening of the occiput with pointing of the frontal bones), was observed in 54 (3%) of the 2,086 fetuses that underwent karyotyping in our unit because of fetal malformations and/or growth retardation. In all 54 cases with a strawberry-shaped skull, there were other fetal malformations; in 43 (80%) fetuses, there was trisomy 18 and in 1 triploidy. Therefore, the ultrasonographic finding of a strawberry-shaped skull should initiate a diligent search for the presence of other markers of trisomy 18 and is a strong indication for fetal karyotyping. However, in the total series of 2,086 fetuses with malformations and/or growth retardation, there were another 40 fetuses with trisomy 18 and 41 with triploidy who did not have a strawberry-shaped skull.

Abnormalities, Multiple↗