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Serge Pissard

Publications and source records attributed to Serge Pissard.

9 recordsLinked to original sources
PubMed2006

Beta-thalassemia in the indigenous population of Brittany: identification of three rare mutations.

Beta-thalassemia mutations were determined in ten Breton probands using a reverse-hybridization method or denaturing gradient gel electrophoresis and sequencing. Six different mutations were found: three from the Mediterranean area and three rare. Mutations responsible for beta-thalassemia in Brittany are quite heterogeneous. The mutation in the initiation codon ATG-->ACG was found in four families and may result from an ancient founder effect, as suggested by the haplotype analysis.

Female↗
PubMed2006

Pyruvate kinase deficiency in France: a 3-year study reveals 27 new mutations.

Pyruvate kinase (PK) deficiency is the most common enzyme defect affecting the glycolytic pathway of the erythrocyte. Usually, it is clinically silent in heterozygotes but serious disorders are described at birth in homozygotes or compound heterozygotes. Including the mutants herein reported, more than 180 mutations of the PK-LR gene have now been identified. This 3-year study was carried out to detect mutations associated with disease-affecting families. Haematological indices, erythrocyte PK and glucose-6-phosphate dehydrogenase activities were measured. Molecular characterisation of the PK gene mutations included restriction enzyme analysis, mutation scanning and gene sequencing. Among the 56 families studied, nine homozygous cases and 41 different mutations were found. Eight mutations involved a splice site, 31 missense mutations were located in crucial domains of the molecule (catalytic site, cleft between the A and C domains, A/A' interface) and two cases of insertion-deletion were found. In total, 20 new mutations modifying the structure of the enzyme and seven affecting a splice site are reported. PK deficiency is an under diagnosed disease. However, deficiency could be life threatening in perinatal period and we report two lethal cases. These results support the characterisation of PK mutations, and show that prenatal diagnosis can identify affected infants and prepare safer conditions for the birth.

Anemia, Hemolytic, Congenital↗
PubMed2005

Two French Caucasian families with dominant thalassemia-like phenotypes due to hyper unstable hemoglobin variants: Hb Sainte Seve [codon 118 (-T)] and codon 127 [CAG-->TAG (Gln-->stop]).

We report two French Caucasian families suffering from dominant thalassemia-like phenotypes due to hyper unstable hemoglobin (Hb) variants. In both cases, molecular analysis revealed a defect localized in the third exon of the beta-globin gene, resulting in dramatic changes of the Hb structure. The first one is a new variant, Hb Sainte Seve, that is associated with a frameshift mutation at codon 118 (-T). In the second family, the disease resulted from a truncated protein due to a stop mutation at codon 127 [CAG-->TAG (Gln-->Stop)]. These two observations are additional evidences of the important role played by helix H in Hb stability: its partial absence, or a large structural modification, seems to be the major reason for the hyper instability of such molecules.

Adult↗
PubMed2005

Severe hemolytic anemia in a Vietnamese family, associated with novel mutations in the gene encoding for pyruvate kinase.

BACKGROUND AND OBJECTIVES: Chronic hemolytic anemias are very frequent diseases in intertropical countries mainly caused by hemoglobin disorders. We studied a Vietnamese family in which a first child suffered from a severe transfusion-dependent anemia. The family requested an antenatal diagnosis during a second pregnancy. To characterize the molecular defect, we studied the family over three generations. DESIGN AND METHODS: Blood from family members was sampled for a full hematologic evaluation, including enzymatic dosage, and DNA analysis was performed for patients displaying pyruvate kinase deficiency (PK-R). Mutation research on the 11 exons of the PKLR gene was done using a scanning method and sequencing. Deletion was evidenced by a Sybergreen based quantitative real time polymerase chain reaction (PCR) and mapped using quantitative multiplex PCR of short fluorescent fragments spread along the whole sequence of the PKLR gene. RESULTS: Hematologic and molecular studies of this severe chronic anemia demonstrated the existence of two defects in the PKLR gene, a new mutation located on exon 7: c.948C->G (N316K) and a large deletion extending from exon 4 to exon 10. INTERPRETATION AND CONCLUSIONS: We describe a family in a south-east Asian country; the proband had severe transfusion-dependent chronic anemia caused by the association between two PKLR gene mutations, PK Saigon (N316K) and PK Viet del 4-10. Severe chronic anemia could be induced by various molecular defects mainly affecting the globin genes. However, even in populations in which hemoglobin diseases are frequent, enzymatic diseases should be considered.

Adult↗
PubMed2004

Compound heterozygosity for two new mutations in the beta-globin gene [codon 9 (+TA) and polyadenylation site (AATAAA-->AAAAAA)] leads to thalassemia intermedia in a Tunisian patient.

More than 200 mutations that are associated with beta-thalassemia (thal) have been found. In most cases, studies to detect a mutation in a patient is made easier because of the existence of geographical sets of mutations that allow the use of a dedicated mutation detection kit. We describe here a patient who originated from Tunisia, in whom we found two as yet unreported mutations, showing that even in a well-studied population a full gene study might be needed to characterize mutation(s).

Adult↗
PubMed2003

FGFR3 and TP53 gene mutations define two distinct pathways in urothelial cell carcinoma of the bladder.

FGFR3 and TP53 mutations are frequent in superficial papillary and invasive disease, respectively. We used denaturing high-performance liquid chromatography and sequencing to screen for FGFR3 and TP53 mutations in 81 newly diagnosed urothelial cell carcinomas. Tumors were classified as follows: 31 pTa, 1 carcinoma in situ, 30 pT1, and 19 pT2-T4. Tumor grades were as follows: 10 G1, 29 G2, and 42 G3. FGFR3 mutations were associated with low-stage (P < 0.0001), low-grade (P < 0.008) tumors, whereas TP53 mutations were associated with high-stage (P < 0.003), high-grade (P < 0.02) tumors. Mutations in these two genes were almost mutually exclusive. Our results suggest that FGFR3 and TP53 mutations define separate pathways at initial diagnosis of urothelial cell carcinoma.

Adult↗
PubMed2003

Hydroxyurea can eliminate transfusion requirements in children with severe beta-thalassemia.

Hydroxyurea (HU) enhances fetal hemoglobin (Hb) production. An increase in total Hb level has been repeatedly reported during HU treatment in patients with sickle cell disease and in several patients with beta-thalassemia intermedia. Effects in patients with beta-thalassemia major are controversial. We now report a marked elevation of total Hb levels with HU that permitted regular transfusions to be stopped in 7 children with transfusion-dependent beta-thalassemia. The median follow-up was 19 +/- 3 months (range, 13-21 months). We conclude that HU can eliminate transfusional needs in children with beta-thalassemia major, which could be particularly useful in countries such as Algeria, where supplies of blood or chelating agents are limited.

Adolescent↗
PubMed2003

A one-step real-time PCR assay for rapid prenatal diagnosis of sickle cell disease and detection of maternal contamination.

INTRODUCTION: Mutations at the codon 6 of the beta-globin gene (hemoglobin [Hb] S and HbC) can be routinely identified by various methods and prenatal diagnosis has been available to affected families for several years. However, the presence of maternal cells in fetal samples constitutes a serious potential source of prenatal misdiagnosis and most methods currently used to detect maternal contamination are based on the analysis of highly polymorphic loci. In addition, these methods are labor intensive and time consuming and risk carry-over contamination. METHOD: We describe here a one-step method for mutation detection that uses fluorescent hybridization probes with melting curve analysis for both simultaneously prenatal diagnosis of sickle cell disease and potential maternal contamination. RESULTS: Retrospective and prospective prenatal diagnosis studies (conducted in 20 and 50 cases, respectively), using both the regular procedure and real-time PCR assay show perfect concordant results. We show in addition, that as little as 5% maternal contamination can be detected and that genotype determinations are unambiguous.

Alleles↗