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Biomedical subjects

F Hentati

Publications and source records attributed to F Hentati.

At least 19 recordsLinked to original sources
PubMed2006

Genetic heterogeneity within a consanguineous family involving the LGMD 2D and the LGMD 2C genes.

The sarcoglycanopathies are a group of autosomal recessive limb girdle muscular dystrophies (AR-LGMD 2) characterised by mutations in gene encoding one of the sarcoglycan subunits. Mutations in SGCA, SGCB, SGCG and SGCD genes are associated with LGMD 2D, 2E, 2C and 2F, respectively. We report three Tunisian patients belonging to the same consanguineous family sharing similar LGMD 2 phenotype but heterogeneous sarcoglycans immunohistochemical patterns. Linkage analysis suggests linkage with the LGMD 2D locus for the two siblings and with LGMD 2C locus for the third patient. Mutation analysis revealed two distinct mutations. A del521T homozygous mutation in exon 6 of the SGCG gene (LGMD 2C), widely distributed in Tunisian patients, was found in one patient, whereas a 157G>A homozygous mutation in exon 2 of the SGCA gene (LGMD 2D) was found in the two siblings. The presence of two distinct genetic forms, LGMD 2C and LGMD 2D in a consanguineous family raises the problem of the complexity of genetic counselling in inbred populations.

Adult↗
PubMed2006

[A comparative study of clinical and paramedical aspects of multiple sclerosis in Tunisia].

INTRODUCTION: Tunisia is considered as a low zone of prevalence for multiple sclerosis (MS). Consequently, only very few studies have taken an interest in this disorder in North Africa. The objective of this study was to compare the clinical and paraclinical parameters and the outcome of the disease in patients affected with MS in Tunisia during two periods (1974-1978 and 1996-2000) and to determine the incidence of the disease and the impact of the use of diagnostic criteria, including the MRI. PATIENTS AND METHODS: We report the results of a retrospective study concerning patients classified with MS and followed in the National Institute of Neurology in Tunis between 1974 and 2000, with 1058 records examined. We divided the patients into two groups belonging to two periods: Group I (1974-1978, 125 patients classified according to the McAlpine criteria) and Group II (1996-2000, 247 patients classified according to Poser's criteria. We compared the clinical and paraclinical parameters of the two groups. RESULTS: The incidence of the disease was evaluated at 1.3 per 100,000 individuals, placing Tunisia in the middle zone of prevalence. There was no significant difference in the mean age of onset (32.4+/-10.1 years) between the two groups. A slight male preponderance was observed in Group I (M/F sex ratio=1.25). The clinical outcome factors were age of onset after 40 years, pyramidal signs as the first symptom, and the progressive forms of the disease. Although Group II had an earlier diagnosis of the disease and a more systematic treatment of relapses, the functional outcome was similar between the two groups. CONCLUSION: MS in Tunisia has the same clinical characteristics and disease outcome as in other countries. The use of MRI allowed earlier diagnosis but did not increase the overall proportion of definite MS.

Adult↗
PubMed2006

[Cardiac involvement in Emery-Dreifuss muscular dystrophy: a case report].

Emery Dreifuss muscular dystrophy (EDMD) is an uncommon hereditary myopathy characterized by 3 symptoms: slow progressive muscular atrophy, muscular contractures and cardiac disease which affect prognosis. We report a 22 year-old patient with EDMD which shows the typical features of the associated dilated cardiomyopathy, ventricular arrhythmia, atrio-ventricular block, atrial standstill then atrial paralysis.

Adult↗
PubMed2005

Allelic heterogeneity of GNE gene mutation in two Tunisian families with autosomal recessive inclusion body myopathy.

Autosomal recessive hereditary inclusion body myopathy (AR-HIBM), with sparing of the quadriceps, is characterized by adult-onset, with weakness and atrophy of distal lower limb muscles, and typical histopathological findings in muscle biopsy. AR hIBM is associated with mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene on chromosome 9p12-13 . We report two unrelated Tunisian families with clinical and pathological features of AR HIBM. One distinct homozygous GNE missense mutation, M712T, previously reported in Middle Eastern Jewish patients, and a newly identified one, L379H, were found in one patient from each family. We conclude that AR HIBM in Tunisia shows an allelic genetic heterogeneity.

Adult↗
PubMed2005

[Behçet's disease associated with peripheral neuropathy].

INTRODUCTION: The involvement of the peripheral nervous system in Behçet's disease is very rare. CASE REPORT: We report a case of a 47-year-old man with a six-year history of Behçet's disease and a two-year history of peripheral nervous system involvement. This patient presented with paraesthesia and weakness of the upper and lower limbs, diarrhea and erectile dysfunction. The electromyogram showed evidence of an axonal sensorimotor neuropathy and the nerve biopsy showed an axonal neuropathy. Routine blood tests were normal, there was no increase of serum creatine kinase, aspartate aminotransfease or lactate dehydrogenase and no signs of hyperthyroidism. Fibroscopy and colonoscopy showed no signs of entero-Behçet. The patient was treated with prednisone, cyclophosphamide and carbamazepine with an improvement of paraesthesia. CONCLUSION: The mechanism of the peripheral neuropathy in Behçet's disease is still unknown, it might be due to vasculitis of the vasa nervorum or to the side effects of colchicine. Our report is particular by the association of sensorimotor and autonomic involvement of peripheral neuropathy in a patient with Behçet's disease.

Anti-Inflammatory Agents↗
PubMed2005

Distinct phenotypes within autosomal recessive ataxias not linked to already known loci.

Autosomal recessive ataxias represent a large group of neurodegenerative disorders characterized by progressive degeneration of central and peripheral nervous systems and a genetic heterogeneity. To analyse clinical, neurophysiological and nerve biopsy findings in 14 Tunisian unrelated families showing linkage exclusion to the known autosomal recessive ataxia loci, 20 Tunisian families with a total of 73 affected subjects were selected on the presence of a clinical phenotype associating a cerebellar ataxia with retained tendon reflexes on at least the index patient. A genetic linkage study was performed with markers spanning the Friedreich ataxia, Spastic ataxia of the Charlevoix-Saguenay, Autosomal recessive ataxia associated with isolated vitamin E deficiency, Ataxia with oculomotor apraxia, Infantile onset spinocerebellar ataxia, Ataxia with Hearing Loss and Optic Atrophy, AT, ATLD, Spinocerebellar ataxia with axonal neuropathy, Cayman ataxia, Cerebellar ataxia with mental retardation optic atrophy and skin abnormalities, Salla syndrome, Marinesco-Sjögren and the Childhood Spinocerebellar Ataxia loci. Out of the 20 families, 4 showed linkage to the spastic ataxia of the Charlevoix-Saguenay locus, one to the Friedreich ataxia locus and one to the Ataxia with oculomotor apraxia locus. Linkage to all tested loci has been excluded in the 14 remaining families. These families were divided into 3 groups according to tendon reflex status in lower limbs which appear as the most obvious distinguishing clinical sign between patients and families: Group A was characterized by brisk tendon reflexes in lower limbs, group B by a homogeneous feature of tendon reflexes with the absence of ankle reflexes and brisk knee reflexes and group C by variable features of tendon reflexes in lower limbs within the same family. Haplotype analysis and Lod score calculation did not show any evidence of linkage to the 16 known loci of cerebellar ataxias. Aim of this study was to reveal the vast clinical phenotypic variability in patients with autosomal recessive ataxia not linked to known loci. Data obtained indicate that detailed clinical and neurophysiological nerve investigations will be essential in order to pool patients within homogeneous subgroups for gene mapping.

Cerebellar Ataxia↗
PubMed2004

Aprataxin gene mutations in Tunisian families.

The authors report clinical and genetic study of 13 patients from three unrelated Tunisian families with an early onset cerebellar ataxia associated with oculomotor apraxia. Cerebellar ataxia with oculomotor apraxia 1 (AOA1) represents a clinically heterogeneous disease caused by mutations in the aprataxin gene. Two novel mutations were identified, the complete deletion of the gene, which seems to not correlate with an increased severity of the disease, and a splice mutation on the acceptor splice site of exon 7.

Adolescent↗
PubMed2004

[Lateral gaze palsy and progressive scoliosis in 4 Tunisian families].

In 1975, Sharpe and Silversides described a neurological entity in a Chinese family. Clinical picture was characterized by paralysis of horizontal gaze, pendular nystagmus and progressive scoliosis. To date, 43 cases have been reported. The pathogenesis remains unclear. The Authors report four Tunisian families with 12 affected individuals. The age of patients ranges from 6 to 34 Years. All examined patients have complete lateral gaze palsy, pendular nystagmus and progressive scoliosis. Blood routine tests, cerebrospinal fluid (CSF), evoked potentials, electromyography (EMG), muscle biopsy, CT scan and cerebral MRI were normal. Autosomal recessive (AR) mode of inheritance is the most probable pattern.

Adolescent↗
PubMed2003

Fukutin-related protein gene mutated in the original kindred limb-girdle MD 2I.

The authors mapped an autosomal recessive form of limb-girdle MD on chromosome 19q13.3 (LGMD2I), further narrowed down the candidate region to 1.1 Mb, and identified one new homozygous mutation in the fukutin-related protein (FKRP) gene on patients of the original Tunisian family. Immunohistochemical and immunoblot analysis showed abnormal expression of alpha-dystroglycan and laminin-alpha2 supporting the hypothesis that FKRP has a role in the interaction between the extracellular matrix components.

Amino Acid Substitution↗
PubMed2003

Phenotype and sarcoglycan expression in Tunisian LGMD 2C patients sharing the same del521-T mutation.

Limb-girdle muscular dystrophy type 2C is an autosomal recessive muscular disorder caused by mutations in the gene encoding the gamma-sarcoglycan subunit. This gamma-sarcoglycanopathy is prevalent in Tunisia where only one homozygous mutation a 521-T deletion has been identified. The aim of this study was to carry out a comparative clinical and immunocytochemical analysis of Tunisian patients sharing the same gamma-sarcoglycan gene mutation. One hundred and thirty-two patients were classified as severe, moderate or mild according to a calculated severity score. Heterogeneous phenotypes between siblings were encountered in 75% of the families. The severity of the disease was not found to be related to the age of onset. Immunohistochemical studies of muscle biopsy showed a total absence of gamma-sarcoglycan, a normal or slightly reduced alpha and delta-sarcoglycans whereas the expression of beta-sarcoglycan was variable. The residual sarcoglycan expression was not related to the clinical phenotype. In conclusion, the phenotypic variability in sarcoglycanopathies in Tunisia seems to involve a modifying gene controlling the course of the disease.

Adolescent↗
PubMed2001

Linkage of a new locus for autosomal recessive axonal form of Charcot-Marie-Tooth disease to chromosome 8q21.3.

We report the clinical and genetic linkage analysis of a large Tunisian family with thirteen affected patients suffering from Charcot-Marie-Tooth disease with pyramidal involvement. The inheritance is autosomal recessive. The clinical phenotype is consistent in all patients. It is characterized by onset during the first decade, a progressive course and distal atrophy in all four limbs, associated with a mild pyramidal syndrome. Nerve biopsy in two patients showed severe axonal neuropathy. Genetic linkage excluded known loci of different genetic forms of Charcot-Marie-Tooth disease, familial spastic paraplegia and familial amyotrophic lateral sclerosis. A significant lod score was obtained with marker D8S286, confirming linkage to chromosome 8q21.3. The clinical syndrome observed in this family seems to correspond to a new genetic form of autosomal recessive Charcot-Marie-Tooth disease.

Adult↗
PubMed2001

Genetic analysis of early onset cerebellar ataxia with retained tendon reflexes in four Tunisian families.

Spinocerebellar ataxias comprise a poorly understood group of inherited degenerative neurological diseases. Attempts to classify hereditary ataxias on the basis of the neurological features or specific clinical signs such as tendon reflex changes have proven to be unsatisfactory. Early onset cerebellar ataxia (EOCA) is generally inherited as an autosomal-recessive trait. Thus far, we do not have accurate answers to several questions about its classification. However, significant clinical heterogeneity observed in four Tunisian families with typical EOCA clinical features reinforces the hypothesis of genetic heterogeneity underlying this phenotype. We have demonstrated that three of the four families studied were not linked to Friedreich's ataxia (FA), vitamin E deficiency ataxia (AVED), and autosomal dominant cerebellar ataxia (ADCA) loci. The fourth family showed homozygosity for a large pathological expansion of GAA repeat in all patients, the parents being heterozygous for this mutation. We have also noted, in the case of the family studied, that there was instability in the transmission of the mutation, along with a phenomenon of anticipation comparable to that observed in dominant triplet repeat diseases. EOCA is thus clinically indistinguishable from FA, yet genetically independent of all known candidate genes. Genetic mapping is required for research into the causal gene and an understanding of the disease's physiopathologic mechanisms.

Adult↗
PubMed2001

The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) are neurodegenerative conditions that affect large motor neurons of the central nervous system. We have identified a familial juvenile PLS (JPLS) locus overlapping the previously identified ALS2 locus on chromosome 2q33. We report two deletion mutations in a new gene that are found both in individuals with ALS2 and those with JPLS, indicating that these conditions have a common genetic origin. The predicted sequence of the protein (alsin) may indicate a mechanism for motor-neuron degeneration, as it may include several cell-signaling motifs with known functions, including three associated with guanine-nucleotide exchange factors for GTPases (GEFs).

Amino Acid Sequence↗
PubMed2001

Effect of vitamin E supplementation in patients with ataxia with vitamin E deficiency.

Ataxia with vitamin E (Vit E) defciency (AVED) is an autosomal recessive disorder caused by mutations of the alpha tocopherol transfer protein gene. The Friedreich ataxia phenotype is the most frequent clinical presentation. In AVED patients, serum Vit E levels are very low in the absence of intestinal malabsorption. As Vit E is a major antioxidant agent, Vit E deficiency is supposed to be responsible for the pathological process. Twenty-four AVED patients were fully investigated (electromyography, nerve conduction velocity (NVC) studies, somatosensory evoked potentials, cerebral computed tomography scan, sural nerve biopsy, genetic studies) and supplemented with Vit E (800 mg daily) during a 1-year period. Clinical evaluation was mainly based on the Ataxia Rating Scale (ARS) for cerebellar ataxia assessment and serum Vit E levels were monitored. Serum Vit E levels normalized and ARS scores decreased moderately but significantly suggesting clinical improvement. Better results were noted with mean disease duration < or = 15 years. Reflexes remained abolished and posterior column disturbances unchanged. Vitamin E supplementation in AVED patients stabilizes the neurological signs and can lead to mild improvement of cerebellar ataxia, especially in early stages of the disease.

Adult↗
PubMed2000

Novel mutations in spastin gene and absence of correlation with age at onset of symptoms.

Autosomal dominant hereditary spastic paraplegia is genetically heterogeneous, with at least five loci identified by linkage analysis. Recently, mutations in spastin were identified in SPG4, the most common locus for dominant hereditary spastic paraplegia that was previously mapped to chromosome 2p22. We identified five novel mutations in the spastin gene in five families with SPG4 mutations from North America and Tunisia and showed the absence of correlation between the predicted mutant spastin protein and age at onset of symptoms.

Adenosine Triphosphatases↗
PubMed2000

Intrafamilial phenotypic variability of Hallervorden-Spätz syndrome in a Tunisian family.

We report clinical features, CT-scan and MRI findings of three siblings with Hallervorden-Spätz disease, one of them followed for more than 20years. Patient 1 presented at age 10 with progressive generalized dystonia. Five years later she had violent dystonic spasms with opisthotonos and marked oro-mandibular involvement. Later, dystonia stabilized and examination showed dysarthria, multiple deformities related to dystonic posturing, retinal degeneration and no cognitive impairment. Cerebral CT-scan showed bilateral pallidal lucencies and T2 cerebral MRI showed the "eye of the tiger" sign.Patient 2 developed delusions and hallucinations at age 18 with acute phases of hetero-aggressivity diagnosed as "schizophrenic" in a psychiatric hospital. At age 20, he developed oromandibular dystonia, severe dysarthria and epilepsy. Cerebral MRI showed the same "eye of the tiger" sign.Patient 3 presented at age 37 with isolated psychiatric features similar to those of patient 2, also diagnosed "schizophrenic" in a psychiatric hospital. Neurological examination showed mild postural tremor of the hands and intermittent cervical dystonia. He was stabilized with neuroleptic treatment.This family shows marked intrafamilial variability of age at onset, symptom at onset (with "schizophrenic" features unusually described and leading to misdiagnosis), clinical presentation (almost entirely dystonic in one patient and almost entirely psychiatric in two others) and course of the disease (slowly progressive in one sibling, rapidly deteriorating in the second and stabilization in the third). Classification and nosology of subtypes of HSD are discussed.

Journal Article↗
PubMed2000

Clinical and genetic study of familial Parkinson's disease in Tunisia.

OBJECTIVE: To determine inheritance patterns and clinical characteristics of familial PD (F-PD) in Tunisia. METHODS: Twenty-one index patients were selected on the basis of typical PD and a family history of PD. The 21 families of the index patients were visited at home, and clinical assessment of all available relatives, a total of 133 individuals, was made. Extensive pedigree data detected 67 additional cases. We ascertained medical history, age, age at onset, first sign at onset, course of the disease, dosage and duration of levodopa (LD) treatment, and associated diseases. One patient from each family was hospitalized to confirm response to LD by evaluation of untreated and treated Unified Parkinson's Disease Rating Scale scores. The sex ratio, transmission pattern, ancestral secondary cases, and segregation ratio (SR) were determined by pedigree analysis. RESULTS: Eighty-eight patients were analyzed (44 men and 44 women; mean age at onset, 39.8 +/- 14.4 years). Pedigree analysis showed 10 single-generation (SG) families (i.e., all affected members belonging to 1 generation) and 11 multigenerational (MG) families (i.e., affected members spanning >1 generation). Parental consanguinity was more frequent in SG families than in MG families. The SR in SG families was 0.23 +/- 0.05, compatible with autosomal recessive (AR) inheritance. Analysis of MG pedigrees showed autosomal dominant (AD) inheritance with reduced penetrance in 9 of 10 families. Age at onset was younger than in sporadic PD. Intrafamilial variability of age at onset, symptom of onset, and clinical course was observed. There was no difference in clinical characteristics between SG and MG families apart from dystonic foot at onset, which was more frequent in SG families. CONCLUSIONS: First, F-PD is clinically similar to sporadic PD apart from younger age at onset. Second, there is intrafamilial and interfamilial variability of all clinical features. Third, F-PD in Tunisia is genetically heterogenous with at least two inheritance patterns: AD and AR.

Adolescent↗