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M Ben Hamida

Publications and source records attributed to M Ben Hamida.

At least 37 records · Page 2Linked to original sources
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↗
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↗
PubMed1996

Limb-girdle muscular dystrophy 2C: clinical aspects.

The LGMD2C linked to chromosome 13q and related to a 35 KDa dystrophin-associated glycoprotein deficiency, is very similar to Duchenne muscular dystrophy with an autosomal recessive inheritance. It is characterized by a variability of the age of onset, the severity of the evolution and the severity of myopathic changes at the muscle biopsy. This variability was also present in the expression of the alpha-sarcoglycan between the same sibships and between different families.

Age of Onset↗
PubMed1995

Mutations in the dystrophin-associated protein gamma-sarcoglycan in chromosome 13 muscular dystrophy.

Severe childhood autosomal recessive muscular dystrophy (SCARMD) is a progressive muscle-wasting disorder common in North Africa that segregates with microsatellite markers at chromosome 13q12. Here, it is shown that a mutation in the gene encoding the 35-kilodalton dystrophin-associated glycoprotein, gamma-sarcoglycan, is likely to be the primary genetic defect in this disorder. The human gamma-sarcoglycan gene was mapped to chromosome 13q12, and deletions that alter its reading frame were identified in three families and one of four sporadic cases of SCARMD. These mutations not only affect gamma-sarcoglycan but also disrupt the integrity of the entire sarcoglycan complex.

Amino Acid Sequence↗
PubMed1995

Physical and genetic mapping of the CMT4A locus and exclusion of PMP-2 as the defect in CMT4A.

We have previously localized one form of the autosomal recessive Charcot-Marie-Tooth disease type 4 (CMT4A) to a 5-cM region of chromosome 8q13-q21. We now report the formation of a 7-Mb YAC contig spanning the region. This contig was used to map nine additional microsatellites and six STSs to this region, and subsequent haplotype analysis has narrowed the CMT4A flanking interval to less than 1 cM. In addition, using SSCP and our physical map, we have demonstrated that the myelin protein PMP-2, mapped by FISH to this region, is not the defect in CMT4A.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Ataxia with isolated vitamin E deficiency is caused by mutations in the alpha-tocopherol transfer protein.

Ataxia with isolated vitamin E deficiency (AVED) is an autosomal recessive neurodegenerative disease which maps to chromosome 8q13. AVED patients have an impaired ability to incorporate alpha-tocopherol into lipoproteins secreted by the liver, a function putatively attributable to the alpha-tocopherol transfer protein (alpha-TTP). Here we report the identification of three frame-shift mutations in the alpha TTP gene. A 744delA mutation accounts for 68% of the mutant alleles in the 17 families analysed and appears to have spread in North Africa and Italy. This mutation correlates with a severe phenotype but alters only the C-terminal tenth of the protein. Two other mutations were found in single families. The finding of alpha TTP gene mutations in AVED patients substantiates the therapeutic role of vitamin E as a protective agent against neurological damage in this disease.

Africa, Northern↗
PubMed1995

Friedreich's ataxia-vitamin E responsive type. The chromosome 8 locus.

The most common autosomal recessive ataxia is Friedreich's ataxia (FA), characterized mainly by an early onset, absent tendon reflexes, deep sensory loss, cerebellar and Babinski signs. Screening the patients from families with classical FA features, we found that some families were excluded from the FA locus on chromosome 9, and are associated to isolate vitamin E deficiency. The similarity of the clinical data between FA with and without vitamin E deficiency was remarkable. The disorder with vitamin E deficiency often confused with FA, is currently known as linked to chromosome 8q. Therefore it is important to test vitamin E levels in all patients suspected to have FA, since the alpha tocopherol supplementation may be efficient in early stages of the disease.

Child↗
PubMed1995

[Cerebral venous thrombosis and arterial infarction in pregnancy and puerperium. A series of 60 cases].

We report a retrospective study of 60 patients aged from 18 to 46 years, pregnant or parturient, with ischemic cerebrovascular accident. The hospital incidence was 3.6 cases per year. The prevalence was 0.70 per 1,000 childbirth in Tunis area. 3/4 of these cerebrovascular accidents occurred in the post partum period and 1/4 in the pregnancy. Gravidic toxemia and sepsis were the most frequent risk factors. The cerebral venous thrombosis (CVT) (55%) were almost as frequent as cerebral ischemic accidents (CIA) 45). We individualized 3 groups of CVT: septic, aseptic, mixed. Among CIA etiologies we noted two cases of cerebral angiopathy of toxemia and one case of peripartum angiography. The mortality rate nul for CIA, was 36% for CVT. The functional sequelae were more severe for CIA.

Adult↗
PubMed1994

Biochemical and immunocytochemical analysis in chronic proximal spinal muscular atrophy.

Immunocytochemical and biochemical analyses were carried out on patients affected by chronic SMA. Three groups of patients were identified. In group I, the muscle presented a fascicular atrophy; a high percentage of atrophic type II fibers; and fibers expressing fast, slow, embryonic, and fetal myosin isoforms. In group II, the muscle was characterized by atrophic fibers and normal/hypertrophic fibers expressing only slow myosin isoforms. In group III, the muscle was characterized by fiber type grouping and fibers coexpressing fast and slow myosin isoforms but never embryonic or fetal MHC isoforms. The muscles of groups I and III contained both fast and slow myosins whereas group II muscles were predominantly slow by immunocytochemical analysis or only slow by biochemical analysis. In view of these results, immunocytochemical and histochemical analyses could help to classify chronic SMA and help to understand the different pathogenic processes which seem to be related to the maturational stage of the muscle at the age of onset of the disease.

Adolescent↗
PubMed1994

Clinical and pathological study of three Tunisian siblings with L-2-hydroxyglutaric aciduria.

This report describes three brothers belonging to a consanguineous family suffering from a progressive neurological disorder associated with L-2-hydroxyglutaric aciduria. Clinically this disorder is characterized by childhood onset, pyramidal signs, cerebellar and pseudobulbar syndromes and epilepsy. Pathological examination of the brain in the oldest patient, who died at the age of 30 years, showed bilateral and diffuse spongiosis with notable cystic cavitations of the cerebral white matter without abnormal storage in neurons and glial cells. We consider that these findings are related to L-2 hydroxyglutaric aciduria. To our knowledge this present case represents the first to be reported with neuropathological examination.

Adolescent↗
PubMed1994

Expression of myosin isoforms and of desmin, vimentin and titin in Tunisian Duchenne-like autosomal recessive muscular dystrophy.

Morphological, morphometrical, histoenzymological, immunocytochemical and biochemical analysis were performed on muscle biopsies taken from patients suffering from tunisian autosomal recessive Duchenne-like muscular dystrophy (TDLMD) selected both by Duchenne-like clinical criteria and by the presence of normal dystrophin. Data were compared to that obtained from DMD biopsies characterized by the absence of dystrophin. The distribution of myosin heavy chain isoforms, desmin, vimentin and titin were determined in type I and type II muscle fibers. The protein pattern appeared to be less affected in TDLMD than in DMD biopsies. The regenerating fibers were mainly but not exclusively type IIC; a noticeable percentage of both type I and type II fibers coexpressed fast and slow MHC isoforms in TDLMD. This percentage was lower than in DMD. The expression of embryonic, fetal, and fast/slow myosin isoforms in type IIC fibers in TDLMD and DMD suggest different fiber type transformations in these two diseases.

Adolescent↗
PubMed1994

Linkage of 'pure' autosomal recessive familial spastic paraplegia to chromosome 8 markers and evidence of genetic locus heterogeneity.

'Pure' familial spastic paraplegias (FSP) are neurodegenerative disorders that are clinically characterized by progressive spasticity of the lower limbs and are inherited as autosomal dominant (DFSP) or autosomal recessive (RFSP) traits. The primary defect in FSP is unknown. Genetic linkage analysis was applied to five RFSP families from Tunisia. In four of these five families tight linkage of the RFSP locus was established to the chromosome 8 markers, D8S260, D8S166, D8S285, PLAT, and D8S279. The RFSP locus in the fifth family was not linked to these markers which provided evidence of genetic locus heterogeneity in RFSP. Identification of the RFSP gene on chromosome 8 will help in understanding the genetic factors in motor neuron degeneration.

Adolescent↗
PubMed1994

Clinical and genetic analysis of a Tunisian family with autosomal dominant cerebellar ataxia type 1 linked to the SCA2 locus.

Autosomal dominant cerebellar ataxias (ADCA) type 1 are a clinically and genetically heterogeneous group of neurodegenerative disorders. We report a large Tunisian ADCA type 1 family in which 17 patients (mean age at onset +/- SD = 35.6 +/- 15.3 years) were examined. There was mean anticipation of 10.3 +/- 15.4 years in this family; anticipation was greater in paternal (28 +/- 8.2 years) than in maternal (2.7 +/- 10.9 years) transmission. Linkage analysis performed with microsatellite markers linked to the spinal cerebellar ataxia 1 (SCA1) locus on chromosome 6p and the SCA2 locus on chromosome 12q excluded linkage to SCA1, but there was close linkage with marker D12S105 (Zmax = 2.51 at theta = 0.00). This result was confirmed by multipoint analysis, which generated a maximal lod score of 3.46 at this locus. Multipoint analysis and haplotype reconstruction reduced the interval containing the SCA2 locus to 6.4 cM, a narrowing of the 35-cM interval in a previously described Cuban SCA2 family with a clinical picture similar to that of our family, including a high frequency of postural and action tremor.

Adult↗
PubMed1994

Phenotype and functional profile of T cells expressing gamma delta receptor from patients with active Behçet's disease.

OBJECTIVE: Our aim was to investigate the TCR gamma delta+ subset in Behçet's disease (BD) inflammatory sites, which better reflects changes associated with the pathologic process than peripheral blood. METHODS: Forty-five patients with active BD, 10 patients with recurrent aphthous ulcers, 12 patients with rheumatoid arthritis, 5 patients with noninflammatory neurologic diseases and 15 healthy individuals were studied. Three monoclonal antibodies TCR delta 1, BB3, and A13 were used to assess the percentage of TCR gamma delta+ in peripheral blood mononuclear cells (PBMC), in bronchoalveolar lavage and cerebrospinal fluid (CSF). CD11a/CD18 was used to study adhesion molecules. TCR gamma delta+ cells isolated by immunomagnetic separation were tested for cytolytic activity against K562 target cells after interleukin 2 stimulation. RESULTS: The PBMC TCR gamma delta BB3+ subset was significantly increased in BD. In BD inflammatory sites, TCR gamma delta+ cells were also present, composed mainly of A13+ cells from these sites also expressed CD11a marker. TCR gamma delta+ cells from inflammatory sites displayed a higher cytotoxic activity than controls, mediated by the A13+ subset. CONCLUSION: The accumulation of cytotoxic TCR gamma delta+ cells at the sites of inflammation suggests their involvement in the local injury process.

Adult↗
PubMed1994

[Congenital fibrolipoma of the mesencephalic protuberation area].

BACKGROUND: Congenital origin of brain fibrolipoma is still debated. A case of such a tumor is presented. CASE REPORT: A female newborn presented with severe hypotonia and macrocephaly that were seen since birth. She died at the age of 2 days. Post-mortem examination showed hydrocephaly due to a tumor located in the mesencephalo-protuberantial region. Histological features of this tumor were those of a fibrolipoma. CONCLUSION: The presence of this brainstem tumor at birth confirms its congenital origin.

Brain Neoplasms↗