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Biomedical subjects

J C Turpin

Publications and source records attributed to J C Turpin.

At least 19 recordsLinked to original sources
PubMed2000

Adult-onset leukodystrophies.

Leukodystrophies are genetic metabolic diseases which generally occur in early childhood at the time of myelination. Surprisingly, these diseases can also occur during adulthood. Adult forms have various clinical presentations which reflect degenerative diseases of the nervous system. The course may last for decades. This contribution describes the main features of adult leukodystrophies and indicates those for which a biochemical and molecular diagnosis are possible. Other articles deal with their differential diagnosis of leukoencephalopathies and with the diagnostic strategy.

Adult↗
PubMed1999

Variable number tandem repeat dopamine transporter gene polymorphism and Parkinson's disease: no association found.

We studied a variable number of tandem repeat polymorphisms in the dopamine transporter gene in search of an association with Parkinson's disease in a French population. Five alleles were detected, consisting of 7, 8, 9, 10 and 11 copies of the 40-base pair repeat sequence, of which the 10-copy allele was the most common. There was no significant difference between the patients and the control subjects in the distribution frequencies of the alleles or genotypes, or in ages at onset in patients between the main allelic classes.

Adult↗
PubMed1997

Juvenile-onset spinal muscular atrophy caused by compound heterozygosity for mutations in the HEXA gene.

Progressive proximal muscle weakness is present both in spinal muscular atrophy (SMA) type III (Kugelberg-Welander disease) and in GM2 gangliosidosis, diseases that segregate in an autosomal recessive fashion. The SMN gene for SMA and the HEXA gene for GM2 gangliosidosis were investigated in a woman with progressive proximal muscle weakness, long believed to be SMA type III (Kugelberg-Welander type). She and her family underwent biochemical studies for GM2 gangliosidosis. Analysis of SMN excluded SMA. Biochemical studies on GM2 gangliosidosis showed deficiency in hexosaminidase A activity and increased GM2 ganglioside accumulation in the patient's fibroblasts. The HEXA gene was first analyzed for the Gly269-->Ser mutation characteristic for adult GM2 gangliosidosis. Since the patient was carrying the adult mutation heterozygously, all 14 exons and adjacent intron sequences were analyzed. A novel mutation in exon 1 resulting in an A-to-T change in the initiation codon (ATG to TTG) was identified. The adult patient is a compound heterozygote, with each allele containing a different mutation. Although mRNA was transcribed from the novel mutant allele, expression experiments showed no enzyme activity, suggesting that neither the TTG nor an alternative codon serve as an initiation codon in the HEXA gene.

Adult↗
PubMed1997

[Juvenile GM2 gangliosidosis with progressive spinal muscular atrophy onset].

GM2 gangliosidosis are caused by a beta-hexosaminidase A enzyme deficiency. Mutations in the gene leaving residual enzyme activity give rise to juvenile and adult forms of the disease which have a great clinical heterogeneity. We report three cases which have been considered for some time as Kugelberg-Welander disease. beta-hexosaminidase A was determined with the sulfated synthetic substrate, 4-méthylumbelliferyl-N-acetylglucosamine 6-sulfate (4-MUGS), which allowed the diagnosis. Two of these cases from one family had normal values of hexosaminidase A in serum as found in the B1 variant. Compound mutations were detected. The B1 variants had a classical B1 mutation (G533-->A) and a new mutation located on exon 11. The patient of the second family had the classical mutation of adult GM2 gangliosidosis (Gly269-->Ser) and a new mutation on exon 1, at the initiation codon.

Adult↗
PubMed1997

[2 familial cases of metachromatic leukodystrophy of late onset].

We report here a familial observation of metachromatic leukodystrophy (MLD) in 2 sisters. The very beginning, with only psychiatric manifestations at adolescence, could be precisely established. The evolution towards a dementia, and the evidence of a pyramidal syndrome oriented later towards a clearly organic disease. A very wide bilateral and symmetrical demyelination was shown by Magnetic Resonance imaging. The deficiency in arylsulfatase A activity oriented towards MLD which was confirmed by metachromatic deposits in the nerve biopsy. Molecular biology evidenced in the two, compound heterozygoty with both the classical mutation of the infantile form with loss of a splicing site at the level of intron 2, and the ileu > Ser 179 mutation frequent in adult forms.

Aged↗
PubMed1996

Mutation frequencies of the cytochrome CYP2D6 gene in Parkinson disease patients and in families.

The frequencies of five mutations of the debrisoquine 4-hydroxylase (CYP2D6) gene (mutations D6-A, B, C, D, and T), corresponding to poor metabolizer (PM) phenotypes, were determined by restriction fragment length polymorphism (RFLP) and polymerase chain reaction (PCR) in 47 patients with Parkinson disease, and compared with the findings in 47 healthy controls. These mutant alleles were about twice as frequent among patients as in controls, with an approximate relative risk ratio of 2.12 (95% confidence interval, 1.41-2.62). There seem to be no significant differences in frequencies of mutant genotypes in patients among gender and modalities of response with levodopa therapy; but frequency of the mutations was slightly enhanced after age-at-onset of 60 years. Mutations D6-B, D, and T were detected in 7 patients belonging to 10 Parkinson pedigrees.

Aged↗
PubMed1996

Methyl bromide intoxication during grain store fumigation.

There have been over 300 cases of methyl bromide poisoning reported in the literature. The first objective of this case report was to bring out an experience with the false belief that work in a closed space is safe when accompanied by the use of a cartridge respirator with activated charcoal. The second objective of this article was to demonstrate the marked toxicity of methyl bromide with the potential to cause long-term neurological damage. Two experienced fumigation workers (equipped with rapidly saturable respiratory cartridges) entered a building where the concentration of methyl bromide was 17g x m-3 instead of the advised 20mg x m-3. They felt rapidly unwell and complained of nausea and shortness of breath, followed for one them by generalized convulsions. Five months later this last man was still bedridden. The other worker had almost no after-effects. The highest bromide level was found in the blood and also in the activated charcoal cartridge of the most injured worker. There was a relationship between methyl bromide level exposure and neurological damage importance.

Adult↗
PubMed1995

Allele doses of apolipoprotein E type epsilon 4 in sporadic late-onset Alzheimer's disease.

Apoliprotein E, type epsilon 4 allele (ApoE-epsilon 4) is associated with late-onset sporadic Alzheimer's disease (AD). We have found that the cumulative probability of remaining unaffected over time decreases for each dose of ApoE-epsilon 4 in sporadic, late-onset French AD. The effect of genotypes on age at onset of AD was analyzed using the product limit method, to compare unaffected groups during aging.

Age of Onset↗
PubMed1995

A new mutation in the HEXA gene associated with a spinal muscular atrophy phenotype.

We describe two adult siblings who had had mild GM2 gangliosidosis since childhood. They presented with spinal muscular atrophy and dysarthria, and one sibling also had mental disturbances. Laboratory studies established the diagnosis of the B1 variant of GM2 gangliosidosis, because the hexosaminidase (Hex) A deficiency was not present upon testing with the unsulfated synthetic substrate 4-methylumbelliferyl N-acetylglucosaminide. HEXA gene analysis proved that the patients are compound heterozygotes for the previously identified G533-->A mutation and for a new mutation, G1171-->A, at exon 11. This new mutation affects a conserved amino acid and results in a Val-->Met substitution at position 391 of the HEXA gene. Full sequence of the alpha-subunit cDNA of Hex A revealed no other mutation. Assays for Hex A activities in patients suspected of having GM2 gangliosidosis should be performed with the sulfated substrate 4-methylumbelliferyl N-acetylglucosamine 6-sulfate.

Adult↗
PubMed1995

[Fibrodysplasia ossificans progressiva. Apropos of a case].

PURPOSE OF THE STUDY: Fibro-dysplasia ossificans progressive is a rare inherited disease, presumably transmitted as an autosomal dominant defect. The high level of spontaneous mutations explains the sporadic cases. Pre symptomatic diagnosis could be actually evoked by the association of progressive ossification of soft tissues with congenital anomalies of bones (metacarpal and metatarsal). The purpose of this study is to report a clinical case with a very severe course. CASE REPORT: A 10-year-old boy developed progressive ossification of muscles and soft tissues in multiple sites neck, back, shoulders, elbows, hips and knees. The clinical course was severe due to the ankylosis of all the joints and the decrease of pulmonary reserve with fixation of the chest wall. A malformation of the great toes facilitated the diagnosis. DISCUSSION: This pattern of heterotopic ossification together with the congenital malformations of the great toes defines the developmental phenotype for fibrodysplasia ossificans. A slow course with successive thrusts occurs. Ossification progressively involves tendons, ligaments and the connective tissue of skeletal muscles. Excision of heterotopic bone is futile as the trauma of the operation can lead to the stimulation of new heterotopic ossification at the operative site. Surgery is only useful for biopsy and histological study reveals bone metaplasia. The mature heterotopic bone is histologically indistinguishable from mature skeletal bone. The non skeletic muscles are characteristically spared from ossification. Premature death often results from respiratory failure due to fixation of the thoracic cage. The pathogenesis and the treatment of the disorder are unknown.

Adolescent↗
PubMed1995

Molecular characterization of Charcot-Marie-Tooth patients in 15 pedigrees from France.

Molecular characterization of Charcot-Marie-Tooth patients in 15 pedigree from France: We collected 15 Charcot-Marie-Tooth (CMT) pedigrees from France. DNA polymorphisms analysis by Southern blotting with probes at the D17S122 locus demonstrated 17p duplication in three CMT1a families and in one sporadic case. Two families affected by CMT2 showed no evidence of the duplication.

Blotting, Southern↗
PubMed1994

Trinucleotide repeat elongation in the huntingtin gene in Huntington's disease patients from 85 French families. The French HD Research Group.

IT15 is a new gene encoding a protein named huntingtin; a polymorphic CAG repeat in the proposed open reading frame of IT15 has been characterized, and an elongation of this repeat has been correlated to Huntington's disease (HD). We have investigated the CAG repeat in the huntingtin gene in 85 unrelated French families with Huntington's disease. In 79 patients (from 60 families, where at least one HD DNA was available) we found repeat lengths of 37 to 100 units, in contrast to 11 to 35 CAG's on normal chromosomes. Comparison of repeat length and age at onset of disease symptoms in 71 individuals confirms an inverse correlation (r = -0.51 for p < 10(-4)) between the age at onset and the number of CAG repeat units.

Adult↗
PubMed1994

Prenatal diagnosis for the unstable CTG repeat sequence in myotonic dystrophy: a retrospective study in a French family.

The results of DNA analysis for the unstable CTG repeat are reported in a french family of myotonic dystrophy. This retrospective study confirms results obtained previously with a linked DNA marker, using the CTG repeat DNA sequence in the same family. The demonstrated possibility of predicting phenotype as well as genotype in prenatal diagnosis is important for such a disorder, were subjects may be severely affected.

Adult↗