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L Surh

Publications and source records attributed to L Surh.

15 recordsLinked to original sources
PubMed2001

Measuring women's preferences for breast cancer treatments and BRCA1/BRCA2 testing.

In establishing decision models in the treatment and prevention of breast cancer, it is important to evaluate patients' preferences for such interventions. The objectives of the present study were: (i) to characterize women's preferences for breast cancer treatments and BRCA1/BRCA2 testing, using the rating scale and standard gamble techniques; and (ii) to identify factors associated with these quality of life indices. Data were collected from women with breast cancer (n = 60), high-risk relatives of women with breast cancer (n = 58), and women in the general population (n = 51). Regardless of group membership, participants favoured treatment and prevention options that involved minimal physical invasiveness. Women with breast cancer rated lumpectomy and radiation treatment more highly than high-risk relatives and women in the general population. Preferences did not differ according to participants' intentions to undergo BRCA testing. Age was the only demographic variable associated with health state preferences. These findings hold implications for the application of patient preferences to clinical decision making.

Attitude↗
PubMed2000

DNA methylation analysis with respect to prenatal diagnosis of the Angelman and Prader-Willi syndromes and imprinting.

The Angelman (AS) and Prader-Willi syndromes (PWS) are clinically distinct neurobehavioural syndromes resulting from loss of maternal (AS) or paternal contributions (PWS) of imprinted genes within the chromosomal 15q11-q13 region. The molecular diagnosis of both syndromes can be made by a variety of techniques, including DNA methylation, DNA polymorphism and molecular cytogenetic analyses. DNA methylation analysis at three major loci (ZNF127, PW71 and 5' SNRPN) has been successfully used for the postnatal diagnosis of AS and PWS. Methylation analysis, in contrast to other techniques, can reliably be used to diagnose all three major molecular classes (deletion, uniparental disomy and imprinting mutation) of PWS, and three of the four major classes of AS. In this study we demonstrate that methylation analysis can also be successfully used in prenatal diagnosis, by examining specimens obtained from amniocentesis and chorionic villus sampling. Correct prenatal diagnoses were obtained in 24 out of 24 samples using the 5' SNRPN locus; 4 out of 15 using the ZNF127 locus; and 10 out of 18 using the PW71 locus. Therefore, our data indicate that although the DNA methylation imprints of ZNF127 and 5' SNRPN arise in the germline and are present in brain, only 5' SNRPN maintains the imprint in tissues suitable for the prenatal diagnosis of AS and PWS.

Amniocentesis↗
PubMed1999

Psychological and social determinants of women's decisions to undergo genetic counseling and testing for breast cancer.

This study examined the demand for breast cancer genetic testing and counseling among Canadian women diagnosed with breast cancer under the age of 50, together with some of the factors predicting both their intentions to be tested and the degree to which they act on their intentions. Participants were 110 women under the age of 50 and comprised of two groups: 1) women diagnosed with breast cancer (BC, n = 60): and 2) an index group of unaffected women from the general population (GP, n = 50). All participants completed a survey that addressed family history of breast and other cancers, demographic variables, knowledge and attitudes about breast cancer, and genetic testing. Members of the BC group were offered genetic counseling and testing for BRCA1 and BRCA2 free of charge. Overall, 60% of participants indicated they would like the test, and 40% either did not want it or were uncertain. Seventy-two percent of women in the BC group wanted to be tested. Of these, only 49% had actually contacted the genetic counselor about testing at follow-up 3-15 months later. Intention to be tested was associated with presence of breast cancer, greater perceived benefits of testing, fewer perceived 'costs' of testing, and higher levels of concern about the risk of relatives developing breast cancer. Actual arranging to meet with the genetic counselor among women in the BC group was associated with fewer perceived costs of having the test. Results suggest a moderate level of interest in gene testing, though intention to be tested may not translate into actual uptake. Women who do choose to have the test may believe the potential 'costs' of using this new genetic technology to be relatively few. This has implications for genetic counselors in terms of providing balanced and complete information to women considering genetic testing for breast cancer susceptibility.

Adolescent↗
PubMed1998

Physician knowledge and attitudes towards molecular genetic (DNA) testing of their patients.

OBJECTIVE: To better define the knowledge and attitudes of practicing physicians about genetics; specifically molecular genetics. Further, to examine differences between four practice specialties and to assess variables that affect both knowledge and attitudes. DESIGN: A mail-in survey was sent to a random sample of non-geneticist physicians, with a second copy sent to non-responders. Questions included sociodemographic variables, sources of current knowledge and education in genetics, clinical experience with genetic disease, self-confidence in providing genetic counseling, attitudes towards referring patients to a genetic center, awareness of molecular genetic testing and attitudes towards its use in clinical practice and population screening. SETTING: Responses were obtained from over 900 practicing physicians in the Canadian province of Ontario (population 10 million). Genetic services are provided through nine major and several outreach centers. Molecular diagnostic services are provided through six provincially funded laboratories. There are no direct costs to the patient for any genetic service. PARTICIPANTS: A random sample of family physicians, obstetricians, pediatricians and internists was surveyed from both private and hospital based practices. RESULTS AND CONCLUSION: Responses varied by specialty, years from graduation, gender, and type of practice. Pediatricians and obstetricians were more knowledgeable about genetics, had more interaction with genetic services and were more supportive of their utility. A major proportion of physicians continue to rely upon undergraduate and medical school courses for knowledge, and the specialties showed different preferences for seeking information. A majority of physicians considered their knowledge of genetics to be adequate, but a minority were confident to provide genetic counseling for simple genetic scenarios. Relatively few had actually made use of DNA diagnostic services and there was relatively poor knowledge of what services were available.

Adult↗
PubMed1995

A recombination event occurring within two complex 5q13.1 microsatellite repeat polymorphisms suggests a telomeric mapping of spinal muscular atrophy.

The gene for the childhood spinal muscular atrophies (SMAs) has been mapped to 5q13.1. The interval containing the SMA gene has been defined by linkage analysis as 5qcen-D5S629-SMA-D5S557-5qter. We have identified a recombination event within this interval on a type-I SMA chromosome. The recombination maps to a region of multilocus microsatellite repeat (MSR) markers, and occurs between different subloci of two such markers, CMS-1 and 7613. While the possibility of a novel mutation caused by the recombination cannot be discounted, we believe when viewed in the context of a similar recombination in a Dutch SMA family, a centromeric boundary at the recombination site for the critical SMA interval is likely. This new proximal boundary would reduce the minimal region harboring the SMA locus from approximately 1.1 Mb to approximately 600 kb.

Alleles↗
PubMed1995

Convergent myotonic dystrophy (DM) haplotypes: potential inconsistencies in human disease gene localization.

Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disease which has been shown to be caused by an unstable trinucleotide repeat located on chromosome 19q. We have conducted extensive haplotype analysis on 105 DM chromosomes using twelve 19q13.2 loci identifying 18 RFLPs, spanning a physical distance of 1.3 Mb containing the DM gene. Three major haplotypes (H1, H2 and H3) comprising 46.7% of the DM chromosomes in our population, were observed. With the exception of H1 and H2 derivatives (H4, H5 and H6), the remainder of the DM chromosomes analyzed were found to have unique haplotypes. Haplotypes H2 and H3 observed exclusively on DM chromosomes of French-Canadian origin contain identical 500-kb core regions. The low frequency of this core haplotype in normal chromosomes (0.8%) is consistent with a mapping of the DM gene within this region. However, the DM mutation is found 160 kb distal to the point of divergence between the two haplotypes. In contrast, the 450-kb region shared by haplotypes H1 and H2 contains the DM mutation. Further analysis of the DM region using a polymorphic microsatellite (GJ-VSSM2; D19S207) located 15 kb distal to the DM mutation revealed strong allelic association of one of the (CA)n repeat alleles to DM; allele 5 was observed on 88.2% of DM chromosomes and 6% of normal chromosomes. The fact that the (CA)n allele 5 was found on all 56 DM chromosomes containing the three major haplotypes indicates that DM chromosomes in our population, including the two French-Canadian haplotypes which have a common region outside the DM gene, are probably derived from the same mutational event.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1994

A multicopy dinucleotide marker that maps close to the spinal muscular atrophy gene.

Spinal muscular atrophy (SMA) is a common autosomal recessive disorder resulting in loss of motor neurons. The interval containing the SMA gene has been defined by linkage analysis as 5qcen-D5S435-SMA-D5S557-5qter. We have isolated a new dinucleotide repeat marker, CATT1, that lies between these two closest markers. The marker CATT1 has 16 alleles and is highly polymorphic. The marker can have 1 to 4 (or more) copies per chromosome, giving rise to individuals with up to 8 (or more) alleles. All of the subloci map between the markers D5S557 and D5S435 and lie in close proximity to one another. The marker CATT1 is linked to the SMA gene with a lod score of Zmax = 34.42 at theta = 0 and crosses all available recombinants. Certain alleles occurred more frequently in either the SMA or normal populations, indicating significant allelic association between CATT1 and the SMA locus. Haplotype analysis combining U.S. and Canadian SMA families reveals that one haplotype group (VII) occurs significantly more frequently in the SMA population than in the normal. This confirms the allelic association of CATT1 with the SMA locus.

Alleles↗
PubMed1994

Two 5q13 simple tandem repeat loci are in linkage disequilibrium with type 1 spinal muscular atrophy.

The gene for the common recessive neuromuscular disorder spinal muscular atrophy (SMA) has been previously mapped to chromosome 5q. We report here linkage disequilibrium analyses of two polymorphic simple tandem repeat (STR) sequences which map into the critical region of 5q13 containing the SMA gene. The polymorphisms presented are constituents of CATT-1, a complex STR which is present in as many as four or more copies per chromosome 5. The PCR can amplify as many as eight CATT-1 products of different sizes from genomic DNA samples due to differing numbers of CA dinucleotides at each STR location (sublocus). Oligonucleotide primers for two of these subloci have been developed for specific PCR assays; a variety of allele sizes can be generated with each assay and, in some cases, no amplification products are detected due to null alleles. The genotyping of 149 SMA Type 1 chromosomes and 142 normal chromosomes from Canadian and American kindreds reveals the presence of significant linkage disequilibrium between the null allele of the sublocus referred to as CATT-40G1 and mutation(s) causing SMA Type 1 (Werdnig-Hoffmann disease). Allele 2 of the second sublocus, CATT-192F7, is also in linkage disequilibrium with SMA Type 1 although the degree of this association is less than that found for CATT-40G1. The proximal and distal STRs from the critical region, D5S435 and D5S351, showed no linkage disequilibrium with SMA. The data presented here will serve as a framework for future linkage disequilibrium analyses, expediting the final stage of the search for the SMA gene.

Alleles↗
PubMed1994

Genetic heterogeneity in spinal muscular atrophy: a linkage analysis-based assessment.

The spinal muscular atrophies (SMAs) are among the most common autosomal recessive disorders. The mapping of the gene responsible for SMA to chromosome 5 has allowed the assessment of genetic heterogeneity in kindreds with a putative diagnosis of SMA. We report linkage analysis of 71 Canadian SMA families (types 1, 2, and 3) using polymorphisms that both flank and are linked to SMA. Data demonstrating nonlinkage to 5q markers were initially obtained in five kindreds; reexamination of the clinical status of these families showed that one fulfilled all the SMA diagnostic criteria, two showed patterns for which a diagnosis of SMA was possible but not conclusive, and two showed patterns for which the diagnosis of SMA appeared unlikely. This results in a degree of genetic heterogeneity between 1.5% and 4.5%. The three kindreds for which SMA appeared either possible or likely were simplex (ie, contained only one affected individual), and therefore the possibility that they represented new mutations could not be discounted. Thus, the significant majority of classic SMA cases are caused by a mutation in the 5q13.1 locus. Low genetic heterogeneity has implications for both genetic counseling and the applicability of conventional and genetic therapies following cloning of the SMA gene.

Adult↗
PubMed1993

Genetic linkage analysis of Canadian spinal muscular atrophy kindreds using flanking microsatellite 5q13 polymorphisms.

The spinal muscular atrophies (SMA) are among the most common autosomal recessive disorders. We have performed linkage analysis using both standard restriction fragment length polymorphisms (RFLPs) as well as microsatellite polymorphisms [Ca(n)] on 49 Canadian SMA families (types 1, 2, and 3) that both flank and are linked to SMA. The closest SMA linkage was observed with the MAP1B locus (zmax = 8.04, theta max = 0.0). Multipoint linkage analysis gave a high probability of SMA mapping between D5S6 and D5S39. Only one family (type 3) that fulfilled our diagnostic criteria for SMA showed nonlinkage with 5q13 markers. This study shows the feasibility of accurate molecular diagnosis of SMA utilizing 5q13 satellite polymorphisms.

Canada↗
PubMed1992

The correlation of age of onset with CTG trinucleotide repeat amplification in myotonic dystrophy.

The gene for myotonic dystrophy (DM) has recently been isolated and amplification of an unstable CTG trinucleotide repeat, located within the DM gene, has been identified in virtually all patients studied to date. A high proportion of DM families who are studied show a progressively earlier age of onset with succeeding generations and, in the few pedigrees reported so far, an increasing degree of amplification of the CTG repeat has been noted to parallel this trend. It has been implicit in several of the original reports on the nature of the changes in the DM gene that knowledge of CTG amplification status at the DM locus of a person will provide useful information concerning prognosis. However, no studies of genotype-phenotype correlation have been reported and there are no specific data on which to base such counsel. In this paper we report the correlation between the degree of CTG amplification and age of onset in 109 DM gene carriers from 17 families. Included are parent-child and sib-sib comparisons which provide a framework in which to incorporate DNA diagnostic studies when counselling subjects and families at risk for DM.

Adolescent↗
PubMed1982

Evidence for a defect of holocarboxylase synthetase activity in cultured lymphoblasts from a patient with biotin-responsive multiple carboxylase deficiency.

We report here the expression of biotin-responsive multiple carboxylase deficiency in cultured lymphoblasts of a patient whose fibroblasts belong to the bio genetic complementation group. Cultured lymphoblasts from the patient lost propionyl-CoA carboxylase (PCC) and beta-methylcrotonyl-CoA carboxylase (MCC) activities at a faster rate than normal cells when grown in biotin-deficient medium. Recovery of normal PCC and MCC activities, which was independent of protein synthesis, required a 2,500-fold higher biotin concentration than that required by normal lymphoblasts. Holocarboxylase synthetase activity was detected in cell-free extracts through the biotinylation of endogenous apo-PCC in the presence of ATP to form active holo-PCC. While the apo-PCC in extracts of normal biotin-starved lymphoblasts could be activated to 28% of maximal activity, extracts of patient lymphoblasts did not exhibit any ATP and biotin-dependent increase in PCC activity. A normal cell extract, cleared of apocarboxylases by immunoprecipitation, stimulated the PCC activity of a patient cell extract 20-fold. These results indicate that the apoenzyme in bio cells is normal and that the defect lies in the holocarboxylase synthetase.

Biotin↗
PubMed1981

Clinical and metabolic abnormalities in a boy with dietary deficiency of biotin.

Dietary deficiency of biotin was documented in an 11-year-old retarded boy as a consequence of a dietary prescription containing raw eggs. Clinical manifestations were alopecia totalis and an erythematous, exfoliative dermatosis. Metabolic characteristics included increased excretion of 3-methylcrotonylglycine, 3-hydroxyisovaleric acid, 3-hydroxypropionic acid, methylcitric acid, and lactic acid, as well as a propensity for the development of ketosis. The activities of propionyl coenzyme A carboxylase and 3-methylcrotonyl coenzyme A carboxylase in extracts of leukocytes were deficient. Treatment with biotin and the removal of raw eggs, which contain the biotin-binding protein, avidin, from the diet led to the reversal of all of the clinical and metabolic manifestations observed.

Alopecia↗