Search PubMed⌕ Search

Biomedical subjects

M A Patton

Publications and source records attributed to M A Patton.

At least 37 records · Page 2Linked to original sources
PubMed2000

Transcervical sampling as a means of detection of fetal cells during the first trimester of pregnancy.

OBJECTIVE: Our aim was to evaluate the detection of fetal cells from transcervical samples by means of fluorescence in situ hybridization analysis. STUDY DESIGN: Forty-seven women undergoing first-trimester termination of pregnancy were recruited for transcervical sampling and 16 were recruited for endocervical mucus aspiration. Subjects were asked to assess the discomfort of the procedure. Fluorescence in situ hybridization analyses were performed with X and Y chromosome-specific probes. Results were compared with those of conventional chromosomal analysis. RESULTS: Male signals (XY) were observed in 19 of 25 male fetuses (76%), and female signals (XX) were observed in 21 of 22 female fetuses. There was a significant variation between operators in cell retrieval. With mucus aspiration only 37.5% of male fetuses were correctly identified. The subjects did not find the procedure uncomfortable and reported that it was comparable to having a cervical smear taken. CONCLUSIONS: Transcervical irrigation correctly identified the sex of 76% of male fetuses, but it still has considerable operator variability. This variability might be reduced by improved catheter design.

Cervix Mucus↗
PubMed2000

Novel mutations in the duplicated region of the polycystic kidney disease 1 (PKD1) gene provides supporting evidence for gene conversion.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common human single-gene disorders, and is the most common inherited form of cystic kidney disease. It is estimated that approximately 85% of ADPKD is due to mutations in the PKD1 gene, which is located on chromosome 16p13.3. Mutation analysis in this gene is difficult, because more than two-thirds of reiterated several times at 16p13.1. In this study, mutation screening in 90 ADPKD patients was carried out on exons in the duplicated region of the PKD1 gene (23-34), using genomic long-range PCR followed by nested PCR and single-strand conformation polymorphism (SSCP), and finally cycle sequencing. Two nonconservative missense mutations were detected in exons 25 and 31, and two conservative mutations were found in exons 24 and 29. A novel splicing mutation, which is expected to cause skipping of exon 30, was detected in one case. Moreover, six intronic variants, three silent variants, and one polymorphic variant were detected in this study. Comparison between some of these changes and published sequences from the homologous genes on 16p13.1, revealed supporting evidence for the gene conversion theory as a mechanism responsible for some of the mutations in the PKD1 gene. Factors likely to facilitate gene conversion in this region of the PKD1 gene are discussed.

Alu Elements↗
PubMed2000

Further delineation of the DOOR syndrome.

Two related sibships from an extended family have been observed with the features of the DOOR syndrome. These features included deafness, onychodystrophy, osteodystrophy, microcephaly, and global developmental retardation with progressive blindness. Seizures, which were associated with hypsarrhythmia, were frequent and difficult to control and ultimately were the cause of death in two patients. An MRI brain scan of case 1 showed a number of abnormalities including markedly reduced myelination. The urine organic acid analysis showed a ten-fold increase of 2-oxoglutarate. In one patient the placenta was noted to have multiple fluid filled cysts, which is a feature reported in other metabolic diseases. It is suggested that there may be genetic heterogeneity in the syndrome, and the presence of increased 2-oxoglutarate is associated with a more severe phenotype which is frequently lethal.

Abnormalities, Multiple↗
PubMed2000

A connexin 26 mutation causes a syndrome of sensorineural hearing loss and palmoplantar hyperkeratosis (MIM 148350).

We report a missense mutation in the connexin 26 gene (GJB2) in a family with an autosomal dominant syndrome of hearing loss and hyperkeratosis. The affected family members have high frequency, slowly progressive, bilateral, sensorineural hearing loss and palmoplantar hyperkeratosis. The mutation causes an amino acid substitution (G59A), which may disrupt a reverse turn in the first extracellular loop of connexin 26. Connexin 26 mutations have been reported in syndromes of deafness and palmoplantar keratoderma. These data provide additional evidence for the role of connexin 26 in syndromes of this type.

Amino Acid Substitution↗
PubMed2000

Hearing impairment in 18q deletion syndrome.

The 18q-syndrome is associated with hearing impairment in 50-80 per cent of cases. The hearing loss may be sensorineural or conductive. A high proportion of cases are associated with narrow or stenosed external auditory canals. This may be a useful clinical pointer to the syndrome. Two cases with impaired hearing are presented in this paper including one case with complex external ear and middle ear malformations. The clinical and audiological features in each case are described.

Adolescent↗
PubMed2000

Study of hemoglobinopathies in Oman through a national register.

OBJECTIVES: A national register of symptomatic hemoglobinopathies has been developed in Oman to facilitate the development of the National Program for the control of genetic blood disorders. METHODS: The information was initially collected retrospectively through hospital records and was refined prospectively with data collected through a survey of pediatricians. The percentages of heterozygotes in different population groups and geographical locations, birth prevalence, age distribution of cases and factors determining frequencies of Hemoglobinopathies in different regions of the country were studied from the register. RESULTS: The register has identified 1757 cases of homozygous Sickle Cell Anemia and 243 cases of beta-thalassemia major in a population of 1.5 million in 1995. Register based national figures of heterozygote carriers approximate 10% for Sickle Cell Anemia and 4% for beta-thalassemia major. CONCLUSION: Defining regional and tribal variations can assist efficient targeting of health resources. This approach provides a simple model for other countries or regions to follow providing there is a health care system that facilitates registration.

Adolescent↗
PubMed1999

Novel nonsense mutation of the endothelin-B receptor gene in a family with Waardenburg-Hirschsprung disease.

Waardenburg syndrome (WS) comprises sensorineural hearing loss, hypopigmentation of skin and hair, and pigmentary disturbances of the irides. Four types of WS have been classified to date; in WS type IV (WS4), patients additionally have colonic aganglionosis (Hirschsprung disease, HSCR). Mutations in the endothelin-3 (EDN3), endothelin-B receptor (EDNRB), and Sox10 genes have been identified as causative for WS type IV. We screened a family with a combined WS-HSCR phenotype for mutations in the EDNRB locus using standard DNA mutation analysis and sequencing techniques. We have identified a novel nonsense mutation at codon 253 (CGA-->TGA, Arg-->STOP). This mutation leads to a premature end of the translation of EDNRB at exon 3, and it is predicted to produce a truncated and nonfunctional endothelin-B receptor. All affected relatives were heterozygous for the Arg(253)-->STOP mutation, whereas it was not observed in over 50 unrelated individuals used as controls. These data confirm the role of EDNRB in the cause of the Waardenburg-Hirschsprung syndrome and demonstrate that in WS-HSCR there is a lack of correlation between phenotype and genotype and a variable expression of disease even within the same family.

Base Sequence↗
PubMed1999

Social, communicational, and behavioral deficits associated with ring X turner syndrome.

We describe the cognitive and behavioral characteristics of five individuals with a ring X chromosome. All subjects had a small active (early replicating) ring X chromosome. The X inactive specific transcript (XIST) locus was confirmed by fluorescent in situ hybridisation (FISH) to be present in all ring X chromosomes. Mental retardation was present in four individuals. All patients with or without mental retardation had a characteristic profile of aggression toward self and others, episodes of screaming, attentional problems, and impulsiveness. Autistic-like features were also present in all individuals and included limited communication, obsessive compulsive behavior, and social difficulties. In some cases the obsessive behavior was extreme and incapacitating. This characteristic behavioral profile may aid the diagnosis and future understanding of ring X.

Adolescent↗
PubMed1999

Splicing mutations in KCNQ1: a mutation hot spot at codon 344 that produces in frame transcripts.

BACKGROUND: Long-QT syndrome is a monogenic disorder that produces cardiac arrhythmias and can lead to sudden death. At least 5 loci and 4 known genes exist in which mutations have been shown to be responsible for the disease. The potassium channel gene KCNQ1, previously named KVLQT1, on chromosome 11p15.5 is one of these. METHODS AND RESULTS: We initially analyzed one family using microsatellite markers and found linkage to KCNQ1. Mutation detection showed a G to C change in the last base of exon 6 (1032 G-->C) that does not alter the coded alanine. Restriction digest analysis in the family showed that only affected individuals carried the mutation. A previous report suggested that a G to A substitution at the same position may act as a splice mutation in KCNQ1, but no data was given to support this hypothesis nor was the transcription product identified. We have shown by reverse-transcription polymerase chain reaction that 2 smaller bands were produced for the KCNQ1 gene transcripts in addition to the normal-sized transcripts when lymphocytes of affected individuals were analyzed. Sequencing these transcripts showed a loss of exon 7 in one and exons 6 and 7 in the other, but an in-frame transcript was left in each instance. We examined other families in whom long-QT syndrome was diagnosed and found another unreported splice-site mutation, 922-1 G-->C, in the acceptor site of intron 5, and 2 of the previously reported 1032 G-->A mutations. All these showed a loss of exons 6 and 7 in the mutant transcripts, validating the proposal that a consensus sequence is affected in the exonic mutations and that the integrity of the base at position 1032 is essential for correct processing of the transcript. CONCLUSIONS: The 6 cases already reported in the literature with the 1032 G-->A transition, the novel 1032 G-->C transversion, and a recent G-->T transversion at the same base show that codon 344 is the second most frequently mutated after codon 341, suggesting at least two hotspots for mutations in KCNQ1.

Child, Preschool↗
PubMed1999

Analysis of the population structure in Oman.

Knowledge of a population structure can be a unique aid in planning genetic services. In order to facilitate the development of genetic services in the Sultanate of Oman, a tribal data base has been developed. The historic records of the beginning of the 19th century were used as the basis and were updated with contemporary information. The tribal data base includes tribal names, locations, and the main 185 major tribes and their subsections. Tribal data can be used for health care planning and the development of disease-specific genetic registers if the hospital records also include the tribal name. They may also provide a useful aid in genetic screening and disease prevention programmes, as when specific mutations are found in rare diseases, it is likely that these will be found to be exclusive to specific tribes, and laboratory testing will be greatly simplified. It is likely that similar data bases could be developed elsewhere in the Middle East and in the immigrant communities in Western Europe.

Journal Article↗
PubMed1998

Neural tube defects and congenital hydrocephalus in the Sultanate of Oman.

A retrospective study was carried out in Oman to determine the incidence of neural tube defects (NTD) and congenital hydrocephalus (CH) and to identify any possible associations. National data retrieved from hospital records revealed the incidence of NTD in Oman to be comparatively low (1.25 per 1000), but the incidence of CH was much higher than that seen in Western Europe (0.44 per 1000) and was found to be associated with high rates of other congenital anomalies and neonatal death. There were no specific environmental factors associated with NTD and high environmental temperatures during the tropical desert summer (temperatures reach 48 degrees C) were excluded as a causative factor. In spina bifida families, later born children were more likely to be affected and there was also an association with increased maternal but not paternal age. Much higher consanguinity rates were noted in families with NTD and CH than in the general population.

Cohort Studies↗
PubMed1998

Outcome of chromosomally normal livebirths with increased fetal nuchal translucency at 10-14 weeks' gestation.

The aim of this study was to determine the outcome of chromosomally normal livebirths with increased fetal nuchal translucency at 10-14 weeks' gestation. Clinical follow up of 89 chromosomally normal livebirths that in fetal life had a minimum nuchal translucency thickness of 3.5 mm and a comparison group of 302 infants whose fetal nuchal translucency thickness at 10-14 weeks of gestation was less than 3.5 mm was performed. Major abnormalities, mainly structural defects of the cardiovascular or skeletal systems, were found in 10.1% (nine of 89) of the group with increased translucency, compared to 2% (five of 302) in those with translucency of less than 3.5 mm (chi2=11.9, p<0.001). Delay in achievement of developmental milestones was observed in one of the infants with increased translucency and in one of the comparison group. The findings of this study show that in chromosomally normal fetuses increased nuchal translucency thickness at 10-14 weeks of gestation is a marker for fetal abnormalities including structural defects and genetic syndromes.

Chromosome Aberrations↗
PubMed1997

Detection of cells of fetal origin from transcervical irrigations.

Twenty-one women (age range 17-38 years) undergoing termination for social reasons in the first trimester were selected. Ultrasound determined the gestation and placental site. A commercially available flexible, sterile plastic tube was advanced to the level of the internal os. Five to eight millilitres of normal saline was injected and then gently aspirated into the tube. Chorionic villus sampling (CVS) or amniocentesis was subsequently performed for back-up sexing. Commercial X and Y probes were used simultaneously for fluorescence in situ hybridization (FISH) study of the cervical washing and back-up samples, XY signals were observed in 10 out of 12 male fetuses and 1 out of 4 female fetuses (false positive), indicating 81.3 per cent correct prediction. Four cervical washing samples did not provide enough cells for FISH. The frequency of cells showing XY signals varied from 3.6 to 47.8 per cent in male-predicted pregnancies. Placental-location, gestational age, or maternal age did not affect the successful retrieval of fetal cells. Trophoblast cells were obtained in a significant number (83 per cent) of pregnant women with male pregnancies by transcervical irrigation in the first trimester. This preliminary part of the study shows the presence of fetal cells in the transcervical samplings and the feasibility of FISH in detecting them; however, further studies are needed to isolate and purify fetal cells.

Abortion, Induced↗