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F Hentati

Publications and source records attributed to F Hentati.

At least 55 records · Page 3Linked to original sources
PubMed1998

Generation of a 3-Mb PAC contig spanning the Miyoshi myopathy/limb-girdle muscular dystrophy (MM/LGMD2B) locus on chromosome 2p13.

Miyoshi myopathy (MM) and limb-girdle muscular dystrophy subtype 2B (LGMD2B) map to the same region on chromosome 2p13. To facilitate the cloning of the defective gene causing these two diseases, we used a combination of chromosome walking and expressed sequence tag (EST) screening and identified 864 P1-derived artificial chromosomes (PACs) whose inserts map to the MM/LGMD2B candidate region and surrounding areas. Among them, 139 are from a chromosome 2-specific PAC library and 725 are from a total genomic PAC library. A 3-Mb contig spanning the candidate region for MM/LGMD2B was assembled. This contig contains 200 PACs, 10 known genetic markers, 5 new polymorphic markers, 57 sequence tagged sites (STSs) generated from PAC end fragments, and 4 random STSs. In addition, we mapped 24 ESTs to this contig and excluded 37 ESTs from the contig, thus eliminating them as candidate MM/LGMD2B genes. The high-resolution, sequence-ready PAC contig for the MM/LGMD2B region provides a backbone for the identification of the disease gene(s) and for clarification of the relationship between the two diseases.

Chromosomes, Human, Pair 2↗
PubMed1998

A gliotoxic factor and multiple sclerosis.

The pathogenesis of multiple sclerosis (MS) is unknown. Searching for possible toxic factors, it was found that 3-day exposure to heat-treated cerebrospinal fluid (CSF) from MS patients caused apoptotic death of astrocytes and oligodendrocytes, but not fibroblasts, myoblasts, Schwann cells, endothelial cells and neurons, in vitro. CSFs from other inflammatory or non-inflammatory neurological diseases showed no toxicity. Exposure of these glial cells to partially purified MS CSF produced DNA fragmentation, apoptotic bodies, chromatin condensation, cell shrinkage, and changes in the levels of known cytokines. A cytotoxic factor, called gliotoxin, was characterized chromatographically as a stable 17-kDa glycoprotein. Since this protein is highly cytotoxic for astrocytes and oligodendrocytes, it may represent an initial pathogenic factor, leading to the neuropathological features of MS, such as blood-brain barrier involvement and demyelination.

Animals↗
PubMed1998

Atypical ataxia telangiectasia with early childhood lower motor neuron degeneration: a clinicopathological observation in three siblings.

We report three brothers belonging to a consanguineous family and suffering from ataxia telangiectasia with severe early neurogenic amyotrophy. Pathological examination of the brain and spinal cord in one of them showed Purkinje cell loss with empty baskets and numerous axonal spheroids, dorsal column demyelination with astrocytic proliferation and severe anterior horn cell degeneration. We consider these pathological findings to be related to Louis-Bar disease. Anterior horn cell changes may be one of the early pathological features in ataxia telangiectasia.

Anterior Horn Cells↗
PubMed1998

Fine localization of the CMT4A locus using a PAC contig and haplotype analysis.

Charcot-Marie-Tooth disease type 4A (CMT4A) is a severe, autosomal recessive peripheral neuropathy linked to chromosome 8q13-q21. We have previously constructed a YAC contig across the CMT4A region and narrowed the disease-flanking interval to approximately three megabases. Subsequently, we constructed a PAC/BAC contig made of 44 clones and mapped 44 new and 30 previous STSs, ESTs, and polymorphic makers to the region. Using 13 polymorphic markers, we have now identified an ancestral haplotype segregating in three families, indicating a common founder mutation. Two ancestral recombination events in this haplotype significantly reduce the minimal candidate region to a minimal trailing path of five PAC/BAC clones, which will now allow direct investigation of candidate genes for CMT4A.

Alleles↗
PubMed1998

Refined mapping and characterization of the recessive familial amyotrophic lateral sclerosis locus (ALS2) on chromosome 2q33.

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative neuromuscular disease that shows familial, autosomal dominant inheritance in 10%-15% of cases. Previous genetic analysis of one large family linked a recessive form of familial ALS (FALS-AR type 3) to the chromosome 2q33-35 region. Using additional polymorphic markers, we have narrowed the size of the linked region to approximately 1.7 cM by linkage and haplotype analysis. We have also established a yeast artificial chromosome contig across the locus that covers an approximate physical distance of 3 million bases. Based on this contig, genes and expressed sequences that map near the 2q33 region have been examined to determine whether they are located within this ALS2 candidate locus. Five identified genes and 34 expressed sequence tags map within the region defined by crossover analysis and merit further consideration as candidate genes for this disease.

Chromosome Mapping↗
PubMed1998

Linkage of a commoner form of recessive amyotrophic lateral sclerosis to chromosome 15q15-q22 markers.

Autosomal recessive familial amyotrophic lateral sclerosis (RFALS) is a rare form of ALS that usually presents at an early age with slow progression of symptoms. RFALS is clinically and genetically heterogeneous and the locus of RFALS type 3 was mapped to 2q33 (ALS2) in a single family. We now report linkage of a more-common form of RFALS to chromosome 15q15-q22 markers (ALS5) and show further genetic locus heterogeneity in RFALS. ALS5 is the locus for most families with RFALS and appears to be present in both North African and European populations.

Age of Onset↗
PubMed1998

LGMD 2E in Tunisia is caused by a homozygous missense mutation in beta-sarcoglycan exon 3.

Four of the currently recognized autosomal recessive limb-girdle muscular dystrophies (LGMD type 2C-F) are caused by mutations in the genes encoding components of the sarcoglycan complex. LGMD 2C, caused by mutations in gamma-sarcoglycan, is prevalent in northern Africa, especially in Tunisia, where this type of muscular dystrophy was originally described. Although the disease initially was assumed to be genetically homogeneous in this region, linkage to the alpha-sarcoglycan locus (LGMD 2D) has also been found. We have now identified the first Tunisian family with beta-sarcoglycanopathy (LGMD 2E), further adding to the genetic heterogeneity of autosomal recessive LGMD in this population. Direct sequencing of the beta-sarcoglycan gene revealed a homozygous mutation (G272-->T, Arg91Leu) in exon 3. This change affects the same arginine residue in the immediate extracellular domain of the protein that was mutated to a proline (G272-->C, Arg91Pro) in a Brazilian family with a severe form of the disease. Immunohistochemical analysis for the sarcoglycan complex demonstrates absence of the known components of the complex in both of these families. We postulate that the immediate extracellular domain of beta-sarcoglycan may be important for the assembly and/or maintenance of this complex, potentially mediated by disulfide-bond formation to another sarcoglycan via the single cysteine residue in that domain.

Adolescent↗
PubMed1998

Electrophysiology and nerve biopsy: comparative study in Friedreich's ataxia and Friedreich's ataxia phenotype with vitamin E deficiency.

The authors report a comparative study of peripheral nerve conductions and nerve biopsy and somatosensory evoked potentials between 15 patients with Friedreich's ataxia and 15 patients with Friedreich's ataxia phenotype with selective vitamin E deficiency. The patients in the two groups are of similar age, age of onset, and clinical phenotype. Peripheral motor nerve action potential amplitude, and conduction velocities are within normal ranges in the two groups. In the Friedreich's ataxia group there is an early and severe peripheral sensory axonal neuronopathy, characterised by an important reduction of the amplitude of sensory action potential, and important loss of myelinated fibres with complete disappearance of large myelinated fibres without any regenerative process. In the Friedreich's ataxia phenotype with selective vitamin E deficiency group there is slight-to-moderate axonal sensory neuropathy with normal to moderate decrease of large myelinated fibre density and important regeneration in nerve biopsy. Somatosensory evoked potentials are markedly involved in the two groups asserting a severe involvement of somatosensory pathway in lumbar, thoracic and cervical spinal cord. These findings suggest that the pathological mechanism involved in the two diseases are different: central peripheral axonopathy in Friedreich's ataxia and central distal axonopathy in Friedreich's ataxia phenotype with selective vitamin E deficiency.

Adult↗
PubMed1998

Methylmalonic acidaemia with bilateral globus pallidus involvement: a neuropathological study.

A 16-month-old boy was hospitalized because of a 1-day history of severe ketoacidosis with lethargy, hypotonia, vomiting, and important dyspnoea. Organic acid assay by gas chromatography-mass spectrometry confirmed the diagnosis of methylmalonic acidaemia (MMA). On the sixteenth day, he developed an acute extrapyramidal disorder. The CT scan of the brain disclosed bilaterally symmetric lucency of basal ganglia. He died at 17 months of age. Post-mortem neuropathological examination, showed severe necrosis with spongiosis, cystic cavitation and numerous lipid-laden macrophages of the globi pallidi, and mild spongiosis of subthalamic nuclei, mammillary bodies, portion of internal capsule adjacent to globus pallidus, superior cerebellar peduncles and tegmentum of brainstem. Pallidal infarction, a focal ischaemic lesion, demonstrates that ischaemia/energy depletion may be important in the etiology of the neuropathology of MMA.

Cobamides↗
PubMed1998

Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy.

Miyoshi myopathy (MM) is an adult onset, recessive inherited distal muscular dystrophy that we have mapped to human chromosome 2p13. We recently constructed a 3-Mb P1-derived artificial chromosome (PAC) contig spanning the MM candidate region. This clarified the order of genetic markers across the MM locus, provided five new polymorphic markers within it and narrowed the locus to approximately 2 Mb. Five skeletal muscle expressed sequence tags (ESTs) map in this region. We report that one of these is located in a novel, full-length 6.9-kb muscle cDNA, and we designate the corresponding protein 'dysferlin'. We describe nine mutations in the dysferlin gene in nine families; five are predicted to prevent dysferlin expression. Identical mutations in the dysferlin gene can produce more than one myopathy phenotype (MM, limb girdle dystrophy, distal myopathy with anterior tibial onset).

Adult↗
PubMed1998

Molecular and clinical correlations in autosomal dominant cerebellar ataxia with progressive macular dystrophy (SCA7).

Spinocerebellar ataxia 7 (SCA7) is caused by the expansion of an unstable CAG repeat in the first exon of the SCA7 gene. We have analyzed the SCA7 mutation in 19 families and one isolated case of various geographical origins, presenting with autosomal dominant cerebellar ataxia with progressive macular dystrophy. The SCA7 CAG repeat was expanded in 77 patients and in 11 at-risk individuals, with alleles containing from 37 to 130 repeats, demonstrating that SCA7 is genetically homogeneous. Repeats on normal alleles contained from 7 to 35 CAGs. There was a strong negative correlation (r = -0.84) between the age at onset and the size of the CAG repeat expansion in SCA7 patients. Larger expansions were associated with earlier onset, a more severe and rapid clinical course, and a higher frequency of decreased vision, ophthalmoplegia, extensor plantar response and scoliosis. The frequency of other clinical signs such as dysphagia and sphincter disturbances increased with disease duration. The mutation was highly unstable during transmission, with a mean increase of 10 +/- 16 CAG repeats, which was significantly greater in paternal (15 +/- 20) than in maternal (5 +/- 5) transmissions. This correlated well with the marked anticipation (19 +/- 13 years) observed in the families. Gonadal mosaicism, observed in the sperm of a patient, was particularly important, with expanded alleles ranging from 42 to >155 CAG repeats. The degree of instability during transmission, resulting mostly in expansions, is greater than in the seven other neurodegenerative disorders caused by polyglutamine expansions.

Adolescent↗
PubMed1998

A clinicopathological observation of Nyssen-van Bogaert syndrome with second motor neuron degeneration: two distinct clinical entities.

OBJECTIVES: To report a novel clinicopathological observation of Nyssen-van Bogaert syndrome. To compare this observation with those previously reported. To discuss the nosological entity of this syndrome. To define the exact etiopathogenic mechanism of the neurogenic amyotrophy occurring at the late stage of the disease. MATERIALS AND METHODS: The patient was a 16-year-old girl who developed loss of vision and deafness at the age of 8. Ataxia with slight cerebellar signs were present by the age of 14. Over the next 2 years, she developed distal weakness and wasting of the legs with depressed ankle reflexes. She died at the age of 16. Deparaffinized sections of the brain, the brain stem, the cerebellum and the spinal cord were stained with haematoxylin & eosin (H&E), Nissl, Woelcke, Bodian, periodic acid-schiff (PAS), Sudan Black and Kluver Barera. Antibodies anti-GFAP, anti-MPB and anti-neurofilaments were used for immunohistochemical stainings following the avidin-biotin-peroxydase complex (ABC) methods. RESULTS: The clinical pictures in our patient are similar to those previously reported in juvenile patients with optico-cochleo-dentate syndrome. Pathological study of the nervous system confirmed the diagnosis of Nyssen-van Bogaert syndrome and also showed a severe anterior horn, posterior horn and Clarke's column nerve cell degeneration with anterior root atrophy. CONCLUSION: From these clinical and pathological data, the authors suggest to include Nyssen-van Bogaert syndrome among the group of multiple system atrophy, propose to divide this syndrome into 2 forms (an early infantile form and a juvenile form) and consider that the neurogenic amyotrophy occurring at the late stage of the disease in juvenile and adult patients is mainly caused by the second motor neuron involvement.

Adolescent↗
PubMed1998

Dihydropteridine reductase deficiency in a large consanguineous Tunisian family: clinical, biochemical, and neuropathologic findings.

We report the case of a large consanguineous Tunisian family of seven siblings suffering from dihydropteridine reductase deficiency with either typical clinical, biochemical, or autopsy findings. Two cousins also were reported to have the same symptoms. This metabolic disorder is characterized by severe microcephaly, psychomotor regression, and progressive basal ganglia calcifications. Dihydropteridine reductase assay on samples collected from the two brothers still alive did not show measurable activity. The sister and four brothers died between the ages of 3 years and 7 years. A neuropathology study done on the sister showed diffuse demyelination throughout the white matter and spongy vacuolation in the subthalamic nuclei, the superior cerebellar peduncles and the tegmentum tracts of the brain stem. The anterointernal part of the putamen was completely necrotic with nearly total nerve cell loss. Abnormal vascular proliferation and calcification of the walls of small, medium, and large arteries and veins, as well as diffusely scattered pericapillary and isolated calcospherites, were seen in this necrotic region. We think that folate deficiency may be involved in the pathogenesis of the basal ganglia calcification.

Basal Ganglia Diseases↗
PubMed1997

Friedreich's ataxia with isolated vitamin E deficiency: a neuropathological study of a Tunisian patient.

The neuropathological findings in a Tunisian patient with Friedreich's ataxia with vitamin E deficiency are reported. The main histological changes are: (1) spinal sensory system demyelination with neuronal atrophy, axonal spheroids and corpora amylacea; (2) neuronal lipofuscin accumulation in the third cortical layer of the cerebral cortex, thalamus, lateral geniculate body, twelfth and ambiguus nuclei, spinal horns and posterior root ganglia. Ultrastructurally, the lipopigments were of uniform granularity without lipid droplets.

Adult↗
PubMed1997

Homozygosity mapping of giant axonal neuropathy gene to chromosome 16q24.1.

Giant axonal neuropathy (GAN) is a rare autosomal recessive disorder described as a symmetrical distal neuropathy, with peripheral axons dilated by accumulation of 10 nm neurofilaments (NF) and a severe course of the disease. The observation of kinky or curly hairs is not a constant finding. The GAN1 locus was localized by homozygosity mapping to chromosome 16 q24.1 in a 3 (4) cM interval flanked by the markers D16S3073 and D16S505 (D16S511) in three non-related Tunisian families, showing a genetic homogeneity in these families. Two point lod-score calculation between the linked haplotype and the disease locus was 14.2 at theta(max) = 0. The patients share a slow course of the disease. The differences in the course of the disease between Tunisian and non-Tunisian patients suggest a possible genetic heterogeneity, which is why the present linkage has been referred to as GAN1. The biochemical defect in GAN1 should help to understand the mechanisms involved in NF accumulations as in other neurological diseases (ALS, SMA).

Axons↗
PubMed1997

Molecular and clinical correlations in spinocerebellar ataxia 2: a study of 32 families.

Spinocerebellar ataxia 2 (SCA2) is caused by the expansion of an unstable CAG repeat encoding a polyglutamine tract. One hundred and eighty four index patients with autosomal dominant cerebellar ataxia type I were screened for this mutation. We found expansion in 109 patients from 30 families of different geographical origins (15%) and in two isolated cases with no known family histories (2%). The SCA2 chromosomes contained from 34 to 57 repeats and consisted of a pure stretch of CAG, whereas all tested normal chromosomes (14-31 repeats), except one with 14 repeats, were interrupted by 1-3 repeats of CAA. As in other diseases caused by unstable mutations, a strong negative correlation was observed between the age at onset and the size of the CAG repeat (r = -0.81). The frequency of several clinical signs such as myoclonus, dystonia and myokymia increased with the number of CAG repeats whereas the frequency of others was related to disease duration. The CAG repeat was highly unstable during transmission with variations ranging from -8 to +12, and a mean increase of +2.2, but there was no significant difference according to the parental sex. This instability was confirmed by the high degree of gonadal mosaicism observed in sperm DNA of one patient.

Adolescent↗
PubMed1996

Recessive Schwartz-Jampel syndrome (SJS): confirmation of linkage to chromosome 1p, evidence of genetic homogeneity and reduction of the SJS locus to a 3-cM interval.

Schwartz-Jampel syndrome (SJS), or chondrodystrophic myotonia, is a rare autosomal recessive disorder characterized by generalized myotonia resulting in a particular, recognizable facies and osteoarticular abnormalities. Some of us have recently shown genetic linkage of SJS to a locus on 1p34-p36.1 in five families. Here, we show by homozygosity mapping and segregation analysis that eight new families are most likely linked to the SJS locus on chromosome 1, confirming the localization of SJS to chromosome 1p and suggesting genetic homogeneity. Recombination events reduced the SJS locus from a genetic interval of 8 to 3 cM, which should facilitate the identification of the SJS gene. Low clinical variability was observed between the studied families, except for osteoarticular abnormalities. Since the severity and the location of osteoarticular abnormalities varied from one individual to another, even in the same families, other factors than the SJS gene itself, genetic or epigenetic, might contribute to the phenotype.

Alleles↗