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Biomedical subjects

M Baiget

Publications and source records attributed to M Baiget.

At least 109 records · Page 6Linked to original sources
PubMed1996

Frequency of intergenerational contractions of the CTG repeats in myotonic dystrophy.

Myotonic dystrophy (MD), an autosomal dominant multisystemic disorder with a high phenotypic variability, is the most common muscular dystrophy in adult life. The mutation underlying DM has been characterized as an expanded CTG trinucleotide repeat sequence in the 3 untranslated region of a protein kinase gene on chromosome 19q13.2-13.3. We have analyzed the presence of CTG intergenerational variations on transmission in parent-child pairs affected with DM. The series includes 90% of all living affected descendants (symptomatic or asymptomatic) from a given myotonic dystrophy (DM) patient. A contraction of the CTG repeat size was observed in ten parent-child pairs (14.1%) and remained unchanged in five (7%) pairs. The number of CTG repeats decreased in 2/30 maternal transmissions (6.7%) and in 8/41 paternal transmissions (19.5%). We found 14 asymptomatic individuals carrying the CTG expansion among the offspring. In six of them, a contraction of the CTG repeat was observed, and in all six cases, the DM allele was paternally transmitted. Since nearly all the asymptomatic family members of DM patients were analyzed in this series, the observed percentage of contractions can be considered more realistic, even though the number of parent-child pairs is small.

Adult↗
PubMed1996

A novel mutation in exon 17 of the beta-subunit of rod phosphodiesterase in two RP sisters of a consanguineous family.

We report the molecular analysis of the beta subunit of the rod phosphodiesterase (PDEB) gene in a consanguineous autosomal recessive retinitis pigmentosa family that shows homozygosity for polymorphisms in the genomic region comprising this gene, and positive linkage between a PDEB marker and the disease. The two affected sisters are homozygous for a T to G transversion in codon 699 of the PDEB gene, leading to the substitution of a leucine by an arginine residue. This change, enclosed in the catalytic domain of the PDEB, could result in a modification of the protein structure preventing the physiological hydrolysis of cGMP.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1996

Autosomal recessive retinitis pigmentosa in Spain: evaluation of four genes and two loci involved in the disease.

Autosomal recessive retinitis pigmentosa (ARRP) is a genetically heterogeneous form of retinal degeneration. The genes for the beta-subunit of rod phosphodiesterase (PDEB), rhodopsin (RHO), peripherin/RDS (RDS) and the rod outer segment membrane protein 1 (ROM1), as well as loci at 6p and 1q, have previously been reported as the cause of ARRP. In order to determine whether they are responsible for the disease in Spanish pedigrees, linkage and homozygosity studies using markers at these loci were carried out on 47 Spanish ARRP families. SSCP analysis was performed to search for mutations in the genes cosegregating with the disease in particular pedigrees. Three homozygous mutations in the PDEB gene were found, thus accounting for 6% of the cases. No other disease-causing mutation was observed in the other genes analysed, nor was significant evidence found for the involvement of the loci at 6p or 1q. On the basis of these data, it is unlikely that these genes and loci account for a considerable proportion of ARRP cases.

Calcium-Binding Proteins↗
PubMed1996

Homozygous myotonic dystrophy: clinical and molecular studies of three unrelated cases.

We report the clinical and molecular study of three unrelated homozygous myotonic dystrophy patients. In the first family, the homozygous patient shows the classical form of the disease with two DM alleles of very different expansion sizes (1000 and 60 repeats). In the second family, the homozygous patient is mildly affected and carries a minimally expanded allele (64 repeats) and a "normal" allele (38 repeats) that increases in size when transmitted. Such an intergenerational expansion of an allele in this range of repeats has not been reported to date. The third homozygous case has late onset bilateral cataracts as the only symptom. She has two minimally expanded alleles (51 and 120 repeats) that showed different intergenerational enlargement during transmission to the next generation.

Adult↗
PubMed1996

Mutational analysis of RAG-1 in lymphoid malignancies.

Illegitimate recombinase activity promoted by the recombination activating RAG-1 and RAG-2 is assumed to be involved in the pathogenesis of the chromosomal translocations observed in lymphoid neoplasias. We analyzed the complete coding region of the RAG-1 gene in patients with lymphoid neoplasis using a multiple PCR-SSCP (single strand conformation polymorphism) strategy. Nine multiple myelomas, 17 non-Hodgkin's lymphomas, 18 acute lymphocytic leukemias, 37 chronic lymphocytic leukemias and 33 non-neoplastic controls were studied. To screen the entire RAG-1 gene we used primers overlapping genomic segments of the RAG-1 coding sequence (nucleotides 87 to 3311). Samples with an abnormal band pattern in the SSCP were cloned and sequenced. Successful amplification was achieved with our protocol. The multiple PCR-SSCP analysis proved to be a feasible and sensitive strategy for studying variations in the sequence of the RAG-1 gene. No mutations other than the three previously reported sequence variations were detected. Although mutations in this gene do not appear to be common in lymphoid neoplasias, it would be interesting to ascertain whether the different variant forms of RAG-1 protein have an abnormal recombinase activity.

DNA Mutational Analysis↗
PubMed1996

[The contribution of molecular genetics to the study of spinal muscular atrophy].

Spinal muscular atrophies constitute a group of hereditary diseases characterized by degeneration of the anterior horn of the spinal cord. Molecular studies began in 1990 with the location of the genome region responsible for the disease in chromosome 5q13. New directions for research were opened in 1995 with the identification of the affected region in the survival motor neuron (SMN) genes and the neuronal apoptosis inhibitory protein genes. A main feature of these genes is that they are duplicate, forming part of two elements (centromeric and telomeric) that include mini-satellites that are also repeated, making this zone particularly unstable. The molecular abnormalities found in patients are a consequence of that instability: gene deletions and conversions in the SMN gene have been described independently of whether symptoms were severe or not. Molecular data make it possible to confirm the clinical diagnosis of most patients and to provide certain prenatal diagnosis for couples that are at high risk of passing on the disorder. Determining both the function of these genes and their pathogenesic role will help to ground new therapeutic strategies that will prevent or detain motor neuron degeneration.

Apoptosis↗
PubMed1995

Factor VIII gene inversions in severe hemophilia A: results of an international consortium study.

Twenty-two molecular diagnostic laboratories from 14 countries participated in a consortium study to estimate the impact of Factor VIII gene inversions in severe hemophilia A. A total of 2,093 patients with severe hemophilia A were studied; of those, 740 (35%) had a type 1 (distal) factor VIII inversion, and 140 (7%) showed a type 2 (proximal) inversion. In 25 cases, the molecular analysis showed additional abnormal or polymorphic patterns. Ninety-eight percent of 532 mothers of patients with inversions were carriers of the abnormal factor VIII gene; when only mothers of nonfamilial cases were studied, 9 de novo inversions in maternal germ cells were observed among 225 cases (approximately 1 de novo maternal origin of the inversion in 25 mothers of sporadic cases). When the maternal grandparental origin was examined, the inversions occurred de novo in male germ cells in 69 cases and female germ cells in 1 case. The presence of factor VIII inversions is not a major predisposing factor for the development of factor VIII inhibitors; however, slightly more patients with severe hemophilia A and factor VIII inversions develop inhibitors (130 of 642 [20%]) than patients with severe hemophilia A without inversions (131 of 821 [16%]).

Blotting, Southern↗
PubMed1995

[Minimal residual disease in chronic myeloid leukemia in patients with long survival after allogeneic bone marrow transplantation].

BACKGROUND: The study of the minimum residual disease in a series of patients diagnosed with chronic myeloid leukemia (CML) treated with non manipulated allogeneic bone marrow transplantation (BMT) reporting a survival longer than 6 months is presented. METHODS: The positivity of the chimeric transcription bcr-abl was studied in 18 long surviving BMT patients. The complementary DNA (cDNA) corresponding to this transcription was amplified by the polymerase chain reaction (PCR) technique. Double internal PCR (PCR nested) was performed to increase the sensitivity of the determination. RESULTS: The first determination was performed in different post BMT stages with a median of 27 months (4-97). Fourteen out the 18 patients were positive for the bcr-abl transcription. On the second determination carried out in 11 cases with a sample obtained 24 months after the first 7 out of the 10 positive cases evaluated presented an identical pattern while the patient who originally was negative, remained so. The original transcription became negative in three patients. Only one of the positive cases developed hematologic relapse during the study period. CONCLUSIONS: Aggressive chemo-radiotherapy does not eradicate the leukemic clone in all patients with chronic myeloid leukemia. The persistence of positive results in a high number of patients with chronic myeloid leukemia in remission for over 6 months after bone marrow transplantation is not predictive of imminent relapse.

Adult↗
PubMed1995

Evidence against involvement of recoverin in autosomal recessive retinitis pigmentosa in 42 Spanish families.

Autosomal recessive retinitis pigmentosa (ARRP) is a degenerative disease of photoreceptors in which defects in the genes encoding rhodopsin, the beta subunit of rod phosphodiesterase (PDEB) and, recently, in the gene for rod cGMP-gated channel, have been reported. However, detailed genetic involvement has not been ascertained in the great majority of cases. Recoverin, another member of the light transduction pathway, is a candidate gene for ARRP. We report the first analyses of the involvement of the recoverin gene (RCV1) in 42 Spanish ARRP families. Linkage and homozygosity studies with an intragenic polymorphism and the close markers D17S945 and D17S786 ruled out RCV1 as the cause of ARRP in 38 pedigrees. In the four remaining families, single strand conformation polymorphism analysis of the recoverin-coding region detected no mutations in the parents or in the affected members. These results strongly suggest that mutations in the RCV1 gene are not responsible for ARRP in these families.

Base Sequence↗
PubMed1995

A frame-shift deletion in the survival motor neuron gene in Spanish spinal muscular atrophy patients.

Spinal muscular atrophy (SMA) is a frequent autosomal recessive disease characterized by degeneration of the motor neurons of the spinal cord causing proximal paralysis with muscle atrophy. The region on chromosome 5q13 encompassing the disease gene is particularly unstable and prone to large-scale deletions whose characterization recently led to the identification of the survival motor neuron (SMN) gene. We now present a genetic analysis of 54 unrelated Spanish SMA families that has revealed a 4-basepair (bp) deletion (AGAG) in exon 3 of SMN in four unrelated patients. This deletion, which results in a frameshift and a premature stop codon, occurs on the same haplotype background, suggesting that a single mutational event is involved in the four families. The other patients showed either deletions of the SMN gene (49/54) or a gene conversion event changing SMN exon 7 into its highly homologous copy (cBCD541, 1/54). This observation gives strong support to the view that mutations of the SMN gene are responsible for the SMA phenotype as it is the first frameshift mutation reported in SMA.

Base Sequence↗
PubMed1995

A novel insertional mutation of a single base on exon 12 of the dystrophin gene.

A new point mutation in exon 12 of the dystrophin gene was identified in a DMD patient using multiple SSCP analysis, which allows the simultaneous study of several exons. The mutation is an A insertion at position 1580 of the cDNA sequence, leading to a stop codon in the translational reading frame. This mutation was not observed in a sample of 70 DMD patients.

Adenine↗
PubMed1995

Contribution of molecular analyses to the estimation of the risk of congenital myotonic dystrophy.

A molecular analysis of the maternal and child CTG repeat size and intergenerational amplification was performed in order to estimate the risk of having a child with congenital myotonic dystrophy (CMD). In a study of 124 affected mother-child pairs (42 mother-CMD and 82 mother-non-CMD) the mean maternal CTG allele in CMD cases was three times higher (700 repeats) than in non-CMD cases (236 repeats). When the maternal allele was in the 50-300 repeats range, 90% of children were non-CMD. In contrast, when the maternal allele was greater than 300 repeats, 59% inherited the congenital form. Furthermore, the risk of having a CMD child is also related to the intergenerational amplification, which was significantly greater in the mother-CMD pairs than in the mother-non-CMD pairs. Although the risk of giving birth to a CMD child always exists for affected mothers, our data show that such a risk is considerably higher if the maternal allele is greater than 300 repeats.

Adult↗
PubMed1995

Comparison of CTG repeat length expansion and clinical progression of myotonic dystrophy over a five year period.

Myotonic dystrophy (DM) is associated with an underlying CTG trinucleotide repeat expansion at a locus on chromosome 19q13.3. We have determined the repeat length in 23 DM patients with varying clinical severity of symptoms and various sizes of repeat amplification. We confirm that as in previous studies there is no strong correlation between repeat length and clinical symptoms but find that the repeat length in peripheral blood cells of patients increases over a time span of five years indicating continuing mitotic instability of the repeat throughout life. Repeat length progression does not appear to be indicative of clinical progression but age probably is. The degree of expansion correlates with the initial repeat size and 50% of the patients with continuing expansions showed clinical progression of their disease symptoms over the five year study period.

Adolescent↗