PubMed Health⌕ Search

Biomedical subjects

R Gagné

Publications and source records attributed to R Gagné.

At least 19 recordsLinked to original sources
PubMed1999

Clinical spectrum of infantile free sialic acid storage disease.

Infantile free sialic acid storage disease (ISSD) is a rare autosomal recessive metabolic disorder caused by a lysosomal membrane transport defect, resulting in accumulation of free sialic acid within lysosomes. Only a few cases have been described. We report on three new cases of ISSD with different modes of presentation: an infant with nephrotic syndrome, a case of fetal and neonatal ascites with heart failure, and a case of fetal ascites with esophageal atresia type III. From these patients and a review of the literature (27 cases total) we draw the following conclusions. 1) "Coarse facies," fair complexion, hepatosplenomegaly, and severe psychomotor retardation are constant findings in this disorder. 2) Nephrotic syndrome occurred in most cases (four in seven) in which renal evaluation was performed. Therefore, ISSD is an important cause of nephrosis in infants with a storage disorder phenotype. 3) Fetal/neonatal ascites or hydrops was the mode of presentation in 13 (60%) of 21 cases. Thus, ISSD enters in the differential diagnosis of hydrops fetalis with a storage disease phenotype. 4) Cardiomegaly was evident in nine cases. 5) Corneae were always clear, and albinoid fundi were reported in five cases. 6) Dysostosis multiplex was not prominent. 7) Bone marrow aspiration could be negative. 8) Death ensued in early infancy with a mean age of 13.1 months. All reported deaths were caused by respiratory infections.

Ascites↗
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↗
PubMed1993

Genetic amniocentesis: a six-years experience in an isolated region of northeastern Quebec (Canada).

The indications, results and outcomes of 508 genetic amniocenteses performed during a 6-years period in Saguenay-Lac-St-Jean (SLSJ), a geographically isolated region of Quebec were reviewed. The geographical distribution of the residences showed that women living in urban communities were more likely to have an amniocentesis than those coming from rural communities. Advanced maternal age was the most frequent indication (62%) while a family history of hereditary disease was an indication in 9%, which is higher than in other published series. The rate of abnormal results in SLSJ was similar to those obtained in other series except for the rate found in amniocenteses done for hereditary diseases (4.3% versus 17.4-45.5%). All the pregnancies for which an abnormal result, but balanced translocations, was found were interrupted or ended spontaneously.

Adolescent↗
PubMed1993

A biochemically distinct form of cytochrome oxidase (COX) deficiency in the Saguenay-Lac-Saint-Jean region of Quebec.

We report the results of biochemical and molecular investigations on a group of patients from the Saguenay-Lac-Saint-Jean region of Quebec who have an unusual form of cytochrome oxidase deficiency and Leigh disease. This group can be distinguished from the classical presentation of cytochrome oxidase deficiency with Leigh disease, by the severity of the biochemical defect in different tissues. The activity in skin fibroblasts, amniocytes, and skeletal muscle of cytochrome oxidase is 50% of normal, while in kidney and heart it is close to normal values. Brain and liver, on the other hand, have very low activities. The defect in activity appears to result from a failure of assembly of the cytochrome oxidase complex in liver, but levels of mRNA for both mitochondrially encoded and nuclear-encoded subunits in liver and skin fibroblasts were found to be the same as those in controls. The cDNA sequence of the liver-specific cytochrome oxidase subunits VIa and VIIa were determined in samples from patient liver and skin fibroblasts and showed normal coding sequence.

Acidosis, Lactic↗
PubMed1992

Assignment of the gene encoding the catalytic subunit C beta of cAMP-dependent protein kinase to the p36 band on chromosome 1.

A cDNA for the human catalytic subunit (C beta) of cAMP-dependent protein kinase (PKA) has been cloned from a testis cDNA library. In the present study, we have determined the chromosomal localization of this gene using a cDNA for C beta as a probe. Southern blot analysis of genomic DNA from human/mouse cell hybrids revealed that the presence or absence of a 20-kb XbaI fragment, which hybridized with the C beta probe, was concordant with the presence of human chromosome 1. In situ hybridization to metaphase chromosome confirmed the somatic cell hybrid data and regionally mapped the C beta gene of PKA to the p36 band on chromosome 1.

Animals↗
PubMed1992

Localization of the human gene for the type I cyclic GMP-dependent protein kinase to chromosome 10.

We have recently characterized cDNAs and genomic DNA fragments for human type I cGMP-dependent protein kinase (cGK). By probing human x hamster hybrid cell lines with a 1.2-kb intron fragment from the human type I cGK gene, we identified a 5.9-kb BglII restriction fragment and localized it to human chromosome 10. In situ hybridization analyses using 3H-labeled cDNA and genomic DNA probes for the human type I cGK to human metaphase chromosomes supported the somatic cell hybrid data and indicated that the gene (PRKG1B; protein kinase, cGMP-dependent) maps to 10p11.2----q11.2.

Blotting, Southern↗
PubMed1992

Localization of the catalytic subunit C gamma of the cAMP-dependent protein kinase gene (PRKACG) to human chromosome region 9q13.

A cDNA for a new catalytic subunit (C gamma) of the cAMP-dependent protein kinase (PKA) was recently isolated from a human testis cDNA library. This subunit was shown to be expressed only in testis, and has so far not been demonstrated in other species. In the present study, we have determined the chromosomal localization of this gene employing a cDNA for C gamma as a probe. Southern blot analysis of genomic DNA from human x mouse somatic cell hybrids allowed us to assign this gene (PRKACG) to human chromosome 9. In situ hybridization to metaphase chromosomes confirmed the somatic cell hybrid data and regionally mapped the C gamma gene of PKA to human chromosome 9q13.

Blotting, Southern↗
PubMed1992

Definition of a small chromosomal rearrangement on chromosome 11p14 by molecular cytogenetics in situ hybridization.

Chromosomal in situ hybridization allows the detection and the definition of single copy DNA segments of very small size. In a particular case, we demonstrate the inactivity of this molecular cytogenetic technique. In this case, karyotype analysis revealed a chromosome 11p+. In situ hybridization of probes PBGD, D11S29, NCAM, and ETSI located at 11q23-qter shows that the extra chromosomal material on chromosome 11p+ is a duplication of the 11q23-qter region.

Abnormalities, Multiple↗
PubMed1991

Cloning and expression of the cDNA encoding human fumarylacetoacetate hydrolase, the enzyme deficient in hereditary tyrosinemia: assignment of the gene to chromosome 15.

Type 1 hereditary tyrosinemia (HT) is an autosomal recessive disease characterized by a deficiency of the enzyme fumarylacetoacetate hydrolase (FAH; E.C.3.7.1.2). We have isolated human FAH cDNA clones by screening a liver cDNA expression library using specific antibodies and plaque hybridization with a rat FAH cDNA probe. A 1,477-bp cDNA was sequenced and shown to code for FAH by an in vitro transcription-translation assay and sequence homology with tryptic fragments of purified FAH. Transient expression of this FAH cDNA in transfected CV-1 mammalian cells resulted in the synthesis of an immunoreactive protein comigrating with purified human liver FAH on SDS-PAGE and having enzymatic activity as shown by the hydrolysis of the natural substrate fumarylacetoacetate. This indicates that the single polypeptide chain encoded by the FAH gene contains all the genetic information required for functional activity, suggesting that the dimer found in vivo is a homodimer. The human FAH cDNA was used as a probe to determine the gene's chromosomal localization using somatic cell hybrids and in situ hybridization. The human FAH gene maps to the long arm of chromosome 15 in the region q23-q25.

Amino Acid Sequence↗
PubMed1990

The human corticosteroid binding globulin gene is located on chromosome 14q31-q32.1 near two other serine protease inhibitor genes.

Human corticosteroid binding globulin (CBG) cDNA fragments were radiolabeled and hybridized in situ to metaphase chromosome preparations. The results localized the CBG gene to the q31-q32.1 region of human chromosome 14. This location also contains the genes for two closely related serine protease inhibitors: alpha 1-proteinase inhibitor and alpha 1-antichymotrypsin. It is therefore likely that these genes evolved by duplication events, and it would appear that this region contains a series of functionally related genes.

Chromosome Banding↗
PubMed1990

11p13 deletion, Wilms' tumour, and aniridia: unusual genetic, non-ocular and ocular features of three cases.

Three cases of Wilms' tumour and sporadic aniridia were followed up for periods ranging from 32 months to seven years. All had a deletion of the short arm of the eleventh chromosome 11p13, including one case with mosaicism, a cytogenetic feature that has not been previously described in the Wilms' tumour and sporadic aniridia association. Unusual non-ocular features found in all patients included tracheomalacia and delayed closure of the anterior fontanelle. In two cases tracheomalacia was responsible for respiratory distress after general anaesthesia. Wilms' tumour developed bilaterally in one patient and on the isthmus of a horseshoe kidney in another patient. In addition to the more commonly observed ocular features the presence of a corneal pannus was noted before 38 months of age in all patients and as early as 17 months in one case. An iridocorneal adherence with an overlying corneal opacity (presumably related to abnormal developmental cleavage of the anterior segment) was noted in one eye only of the mosaicism case.

Anesthesia, General↗
PubMed1990

Localization of the human sex hormone-binding globulin gene (SHBG) to the short arm of chromosome 17 (17p12----p13).

Human sex hormone-binding globulin (SHBG) is a plasma steroid transport protein which is known to be encoded by an autosomal gene. We have hybridized two separate cDNA probes, corresponding to the 5' and 3' portions of the coding sequence for SHBG, to human metaphase chromosomes in situ. In this way, the SHBG gene has been localized to the p12----p13 bands of chromosome 17.

Chromosome Banding↗
PubMed1990

Fine mapping of the long arm of human chromosome 11 by in situ hybridization using different translocations, including the t(11;22) of Ewing sarcoma.

The progesterone receptor gene (PGR), the gene coding for porphobilinogen deaminase (PBGD), the gene coding for a neural cell adhesion molecule (NCAM), the oncogene ETS1, and the anonymous genomic sequence D11S29 have been previously located on the long arm of chromosome 11. However, gene localizations obtained with different gene-mapping procedures have led to occasional discrepancies. To localize these genes more precisely, we hybridized five human DNA sequences with different chromosomal rearrangements, including four balanced and one unbalanced translocations. We show here that the order of these five sequences is cen-PGR-PBGD-DIIS29/NCAM/ETS1-tel.

Cell Adhesion Molecules, Neuronal↗
PubMed1990

More than one mutant allele causes infantile Tay-Sachs disease in French-Canadians.

Two Tay-Sachs disease (TSD) patients of French-Canadian origin were shown by Myerowitz and Hogikyan to be homozygous for a 7.6-kb deletion mutation at the 5' end of the hexosaminidase A alpha-subunit gene. In order to determine whether all French-Canadian TSD patients were homozygotes for the deletion allele and to assess the geographic origins of TSD in this population, we ascertained 12 TSD families of French-Canadian origin and screened for occurrence of mutations associated with infantile TSD. DNA samples were obtained from 12 French-Canadian TSD families. Samples were analyzed using polymerase-chain-reaction (PCR) amplification followed by hybridization to allele-specific oligonucleotides (ASO) or by restriction analysis of PCR products. In some cases Southern analysis of genomic DNA was performed. Eighteen of the 22 independently segregating mutant chromosomes in this sample carried the 7.6-kb deletion mutation at the 5' end of the gene. One chromosome carried the 4-nucleotide insertion in exon 11 (a "Jewish" mutation). In this population no individuals were detected who had the substitution at the splice junction of exon 12 previously identified in Ashkenazi Jews. One chromosome carried an undescribed B1 mutation; this allele came from a parent of non-French-Canadian origin. Patients in three families carried TSD alleles different from any of the above mutations. The 5' deletion mutation clusters in persons originating in southeastern Quebec (Gaspé) and adjacent counties of northern New Brunswick.

Alleles↗
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

Characterization of two mRNA species encoding human estradiol 17 beta-dehydrogenase and assignment of the gene to chromosome 17.

Using two 33-mer synthetic oligonucleotides derived from the amino acid sequence of the catalytic site of estradiol 17 beta-dehydrogenase (E2DH) and polyclonal antibodies raised against the enzyme purified from human placenta, clones were isolated from a lambda gt11 human placental cDNA library. A 327-amino acid sequence was deduced from cDNA sequencing. Two mRNA species have been identified in poly(A)+ RNA from human placenta, a major species migrating at 1.3 kb while a minor one is found at approx. 2.2 kb. Primer extension and S1 nuclease analysis indicate that the major mRNA species starts 9-10 nucleotides while the minor mRNA starts 971 nucleotides upstream from the ATG initiating codon, respectively. Sequence analysis of the longest cDNA clone (2092 bp) shows that it possesses identical coding and non-coding sequences in the regions of overlap with the shorter cDNA clones. The 32P-labeled 5' non-coding fragment hybridizes only to the 2.2 kb band, thus providing evidence for the existence of two distinct mRNA species which differ in their 5' noncoding regions. Using hp E2DH-36 cDNA as a probe for in situ hybridization of translocated chromosomes, the human E2DH gene was localized to the q11-q12 region of chromosome 17.

17-Hydroxysteroid Dehydrogenases↗