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Biomedical subjects

C Laberge

Publications and source records attributed to C Laberge.

At least 19 recordsLinked to original sources
PubMed2006

Clinical characteristics of myotonic dystrophy type 1 patients with small CTG expansions.

The authors report a genotype-phenotype correlation study in 102 patients with myotonic dystrophy type 1 carrying small CTG repeat expansions. Most patients carrying 50 to 99 CTG repeats were asymptomatic, except for cataracts. Myotonia, weakness, excessive daytime sleepiness, and myotonic discharges at EMG were significantly more present in the patients with 100 to 200 CTG repeats. These findings highlight different outcomes related to the expansion size, even among small CTG expansions.

Adolescent↗
PubMed2004

Strategies for consulting with the community: the cases of four large-scale genetic databases.

Large-scale genetic databases are being developed in several countries around the world. However, these databases depend on public participation and acquiescence. In the past, information campaigns have been waged and little attention has been paid to dialogue. Nowadays, it is important to include the public in the development of scientific research and to encourage a free, open and useful dialogue among those involved. This paper is a review of community consultation strategies as part of four proposed large-scale genetic databases in Iceland, Estonia, United Kingdom and Quebec. The Iceland Health Sector Database and Estonian Genome Project have followed a "communication approach" in order to address public concerns, whereas, UK Biobank and Quebec CARTaGENE have chosen a "partnership approach" to involve the public in decision-making processes. Following a comparison of community consultation strategies, the main concerns of the public are examined as well as the challenges of involving communities. Importantly, reported across all groups is the concern for confidentiality, respect of the individual, transparency, and the donor's right to access to their own result. However, even if researchers demonstrate a willingness to respect values such as fair representation, transparency and accountability, there is still a risk that the public will mistrust researchers and simply will not participate in sufficient numbers. Complications may arise when individual and community interests conflicts. The implementation of a partnership approach is definitely involving and costly; however, if used properly, this method can improve both participation and so database development.

Community Participation↗
PubMed2002

Sibship stability of genotype and phenotype in myotonic dystrophy.

Myotonic dystrophy (DM1) is caused by an unstable CTG repeat expansion. Despite the evidence of birth order effect in congenital DM1, the expansion's dynamics among sibships is still unknown. The objective of this study was to determine phenotype and CTG repeat size variability in DM1 sibships, and to investigate their predictive values. We compared 86 sib pairs for CTG repeat, 61 for age at onset and 89 for DM1 phenotype. CTG repeats remained stable for 66 of the 86 sib pairs, including 25 of 27 maternal transmissions and 30 of 42 paternal transmissions. Variations of less than 10 years in the age at onset were observed in 44 of 61 sib pairs, including 16 of 18 maternal transmissions and 19 of 28 paternal transmissions. The same phenotypic severity or a variation of only one class was observed among 86 of the 89 sib pairs, including all of the 35 maternal transmissions and 30 of the 33 paternal transmissions. Birth order, intergenesic interval, oldest sib's CTG repeat or parental age and CTG repeat did not exert any significant influence. These results suggest that genotype and phenotype remained stable among sibs, although the paternal origin of the mutation seemed to reduce the predictability of the severity.

Adolescent↗
PubMed1999

Genome-wide search for linkage of bipolar affective disorders in a very large pedigree derived from a homogeneous population in quebec points to a locus of major effect on chromosome 12q23-q24.

We completed a genome-wide scan for susceptibility loci for bipolar affective disorders in families derived from a rather homogeneous population in the Province of Québec. The genetic homogeneity of this population stems from the migration of founding families into this relatively isolated area of Québec in the 1830s. A possible founder effect, combined with a prevalence of very large families, makes this population ideal for linkage studies. Genealogies for probands can be readily constructed from a population database of acts of baptism and marriage from the early 1830s up to the present time (the BALSAC register). We chose probands with a DSM III diagnosis of bipolar affective disorder and who may be grouped within large families having genealogical origins with the founding population of the Saguenay-Lac-St-Jean area. Living members (n approximately 120) of a very large pedigree were interviewed using the Structured Clinical Interview for DSM III (SCID I), SCID II, and with a family history questionnaire. A diagnostic panel evaluated multisource information (interview, medical records, family history) and pronounced best-estimate consensus diagnoses on all family members. Linkage, SimAPM, SimIBD, and sib-pair analyses have been performed with 332 microsatellite probes covering the entire genome at an average spacing of 11 cM. GENEHUNTER and haplotype analyses were performed on regions of interest. Analysis of a second large pedigree in the same regions of interest permitted confirmation of presumed linkages found in the region of chromosome 12q23-q24.

Bipolar Disorder↗
PubMed1998

Socioeconomic geographical links to human immunodeficiency virus seroprevalence among childbearing women in Montreal, 1989-1993.

BACKGROUND: To describe the socioeconomic profiles of geographical areas on Montreal Island in which human immunodeficiency virus (HIV) seropositive women delivering live births between 1989 and 1993 reside. METHODS: Leftover dried blood spot filter paper specimens collected from newborns were irretrievably unlinked from identifying information prior to testing. Seroprevalence estimates were calculated based on Western blot confirmed positive samples. Using data from the Canadian census, Revenue Canada, and provincial birth records, the socioeconomic characteristics of postal zones in which seropositive mothers reside were described. RESULTS: Montreal Island had an overall 5-year HIV seroprevalence rate estimate of 16.6 (95% CI: 14.1-19.3) per 10000 childbearing women. Areas in which at least one seropositive woman gave birth had lower mean infant birthweights and higher percentages of single mothers and single-parent families. The HIV-positive neonatal blood specimens were more likely to originate from areas where a higher proportion of residents reported less education, greater unemployment, and lower income. CONCLUSIONS: Higher HIV infection rates were found among childbearing women from lower socioeconomic areas of Montreal. Increased understanding of the relationship between socioeconomic status and HIV acquisition and transmission is required to inform the development of targeted HIV prevention programmes.

Adult↗
PubMed1996

A case of tyrosinaemia type I with normal level of succinylacetone in the amniotic fluid.

Prenatal diagnosis of tyrosinaemia type I can be achieved in cultured amniotic cells and in chorionic villus material by testing the activity of fumarylacetoacetate hydrolase and by DNA analysis, and in amniotic fluid by succinylacetone measurement. This specific metabolite can be measured either by gas chromatography-mass spectrometry or by delta-aminolevulinate dehydratase inhibition assay. In a series of 65 at-risk cases tested with the enzyme inhibition assay, one case out of the 18 with the disease had a normal level of succinylacetone. This case is presented.

Amino Acid Metabolism, Inborn Errors↗
PubMed1990

HIV infection among Quebec women giving birth to live infants.

This is the first anonymous unlinked seroprevalence study in Canada to use serum samples from newborns to determine the seroprevalence rate of human immunodeficiency virus (HIV) infection among childbearing women. Of the 68,808 samples tested 42 were confirmed as positive, for an overall crude seroprevalence rate of 6.1 per 10,000 live births (95% confidence interval [CI] 4.4 to 8.3), or 1 woman in 1638. Women who lived on Montreal island had an overall rate of 17.9 per 10,000 live births (95% CI 12.2 to 25.4), or 1 woman in 559. We observed a significant association between revenue index and seroprevalence; the rates were as high as 46.4 per 10,000 live births (95% CI 18.7 to 95.3), or 1 woman in 216, for Montreal island postal code areas with revenue indexes 20% or more below the provincial median. Extrapolation of the data suggested that 56 women with HIV infection gave birth to a live infant during 1989 in Quebec. Even though attempts to generalize the data from childbearing women to women of childbearing age have an inherent conservative bias, the results of our study suggest that 988 women (95% CI 713 to 1336) aged 15 to 44 years in Quebec had HIV infection in 1989. The actual number is likely substantially higher. The need for well-designed, creative interventions to prevent further HIV transmission to women is evident. Planning for the provision of medical and psychosocial services sensitive to specific needs of women who are already infected should start immediately.

Adolescent↗
PubMed1990

Tight linkage of creatine kinase (CKMM) to myotonic dystrophy on chromosome 19.

The myotonic dystrophy (DM) gene is localized to the proximal long arm of chromosome 19. There have been reports of tight linkage to a number of chromosome 19 markers, including APOC2 and creatine kinase muscle type (CKMM), but they did not establish orientation of the 2 markers to DM. We screened several large multi-generational DM families for linkage to a series of chromosome 19 markers including CKMM. CKMM is tightly linked to DM in these data with z(theta) = 28.41; theta = 0.01. Analysis of cross-over data indicates CKMM is on the same side and closer to DM than APOC2. Thus, CKMM is a useful probe for carrier detection studies in presymptomatic individuals as well as for prenatal diagnosis.

Chromosome Mapping↗
PubMed1990

Recurrent mutation, gene conversion, or recombination at the human phenylalanine hydroxylase locus: evidence in French-Canadians and a catalog of mutations.

The codon 408 mutation (CGG----TGG, Arg----Trp) in exon 12 of the phenylalanine hydroxylase (PAH) gene occurs on haplotype 1 in French-Canadians; elsewhere this mutation (R408W) occurs on haplotype 2. A CpG dinucleotide is involved. The finding is compatible with a recurrent mutation, gene conversion, or a single recombination between haplotypes 2 and 1. A tabulation of 20 known mutations at the PAH locus reveals three instances of putative recurrent mutation.

Alleles↗
PubMed1990

Different molecular basis for fumarylacetoacetate hydrolase deficiency in the two clinical forms of hereditary tyrosinemia (type I).

Hereditary tyrosinemia is characterized by a deficiency of the enzyme fumarylacetoacetate hydrolase (FAH; E.C.3.7.1.2), the last enzyme in the catabolic pathway of tyrosine. FAH was purified from rat and human liver and was used to immunize rabbits. Specific antibodies were used to probe protein extracts of livers and other tissues of normal and tyrosinemic patients. No immunoreactive FAH band was observed on immunoblots of liver, kidneys, and lymphocytes from patients presenting with the acute form of hereditary tyrosinemia. Patients with the chronic form had immunoreactive FAH at a level approximately 20% of normal liver values, which was correlated with the measured enzymatic activity. Immunoblot analysis of aborted fetal tissues revealed normal FAH immunoreactivity in normal liver and kidneys. No FAH immunoreactivity was found in liver and kidneys of tyrosinemic fetuses. The presence of FAH immunoreactivity in normal fetal tissues suggests that deficient FAH activity in tyrosinemia is not simply related to a developmentally regulated expression of the enzyme. By this immunoblot assay, FAH was detected in most human tissues, with maximal immunoreactivity in liver and kidneys and with only trace amounts in chorionic villi and cultured amniocytes. These data confirm that the primary defect in the acute form of hereditary tyrosinemia is an absence of FAH. Moreover, these data suggest that both clinical forms of the disease have a different molecular basis.

Amino Acid Metabolism, Inborn Errors↗
PubMed1990

Fumarylacetoacetase measurement as a mass-screening procedure for hereditary tyrosinemia type I.

Fluorometric quantitative tyrosine determination on dried-blood spots is the primary neonatal screening test used for tyrosinemia type I (HT) in the province of Quebec. Succinylacetone determination on these same spots is used as the complementary test when the tyrosine level is higher than a given threshold. This procedure has proved to be less discriminant over the past few years because of changes in newborn feeding and because of early discharge of newborns from the nursery. We have developed an enzyme-linked immunosorbent assay (ELISA) to measure the deficient enzyme in HT in dried-blood spots. Fumarylacetoacetase (FAH) (E.C.3.7.1.2) was measured retrospectively by an ELISA on 25 dried-blood samples from proven patients with HT and prospectively in 72,000 specimens received in the neonatal screening program. In this pilot project, FAH was measured first, and, if necessary, succinylacetone was determined as the complementary test. All 25 samples from proven patients and specimens from four other patients detected in the pilot study have shown almost complete absence of FAH in dried-blood samples. At a cutoff level of 12.5% of normal adult blood spotted on the same type of paper, only 30 other cases disclosed FAH levels low enough to warrant succinylacetone measurement but had no detectable succinylacetone. The false-positive rate is thus 1:2,400 with this primary ELISA. However, blood transfusion in newborns prior to blood collection on filter paper may yield false-negative tests, since FAH is present in erythrocytes of normal donors.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Metabolism, Inborn Errors↗
PubMed1990

Oral loading of homogentisic acid in controls and in obligate heterozygotes for hereditary tyrosinemia type I.

Homogentisic acid (HGA) (50 mg/kg) was given orally to 22 obligate heterozygotes for hereditary tyrosinemia type 1 (HT) and to 11 controls. After 1 h the mean +/- standard error (SE) plasma level of HGA was 30.42 +/- 1.41 micrograms/ml in carriers and 19.29 +/- 1.62 in controls. Mean +/- SE fasting delta-amino-levulinate dehydratase (delta-ALD) was 40.05 +/- 1.79 m microM/min/g Hb in carriers, much lower than the 60.81 +/- 5.11 found in controls. After 3 h this difference in levels of delta-ALD remained, with mean +/- SE values of 25.70 +/- 2.89 m microM/min/g Hb in carriers, compared with 48.83 +/- 5.37 in controls. Three-hour mean +/- SE excretion of fumarylacetone "equivalent" [FAc] in urine in carriers, 51.597 +/- 5.580 micrograms/mg/creatinine, was significantly higher than the 27.941 +/- 5.916 in controls. Three-hour excretion of succinylacetone "equivalent" [SAc] was also significantly higher in the urine of carriers. FAc in 3-h urine was identified by thin-layer chromatography and confirmed by gas chromatography/mass spectrometry. Multivariate stepwise discriminant analysis showed that the inclusion order of significant variables was as follows: HGA levels at 1 hr, fasting level of delta-ALD, residual level of HGA at 3 h, and 3-h excretion of [FAc]. Non-significant variables were HGA tolerance, levels of delta-ALD at 3 h, sex, and 3-h excretion of [SAc].(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Metabolism, Inborn Errors↗
PubMed1989

DNA sampling and informed consent.

Standard consent forms for blood and tissue sampling are inadequate for DNA sampling. However, creating new and separate forms for each type of activity associated with DNA analysis (banking, linkage analysis and genetic diagnosis) tends to dissociate the participant from what is essentially a medical continuum. Furthermore, DNA sampling involves the sharing of samples and data among centres. To ensure patient control throughout this multifaceted process, we have developed an integrated approach to obtaining consent for DNA sampling at each level of participation. Movement from one level to another is reflected in the choices offered to participants. This inclusive approach is based on the underlying principle of informed consent, namely the respect for individuality, confidentiality and freedom of choice. This approach should help practitioners of medical genetics recognize the medical context of DNA sampling.

Canada↗