Biomedical subjects

A Benomar

Publications and source records attributed to A Benomar.

At least 37 records · Page 2Linked to original sources

PubMed1999

A locus for an axonal form of autosomal recessive Charcot-Marie-Tooth disease maps to chromosome 1q21.2-q21.3.

Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of disorders that affect the peripheral nervous system. Three loci are known for the autosomal dominant forms of axonal CMT (CMT2), but none have yet been identified for autosomal recessive axonal CMT (ARCMT2). We have studied a large consanguineous Moroccan ARCMT2 family with nine affected sibs. The onset of CMT was in the 2d decade in all affected individuals who presented with a severe motor and sensory neuropathy, with proximal muscle involvement occurring in some patients. After exclusion of known loci for CMT2 and for demyelinating ARCMT2, a genomewide search was performed. Evidence for linkage was found with markers on chromosome 1q. The maximum pairwise LOD score was above the threshold value of 3.00, for markers D1S514, D1S2715, D1S2777, and D1S2721, and it reached 6.10 at the loci D1S2777, D1S2721, and D1S2624, according to multipoint LOD-score analysis. These markers defined a region of homozygosity that placed the gene in a 4.4-cM interval. Moreover, a recombination event detected in an unaffected 48-year-old individual excludes the D1S506 marker, thereby reducing the interval to 1.7 cM. In addition, the P0 gene, an attractive candidate because of both its location on chromosome 1q and its role in myelin structure, was excluded by physical mapping and direct sequencing.

Adolescent↗

PubMed1999

Polyradiculoneuropathy revealing a solitary plasmacytoma of the ilium. A new case-report.

Neurological manifestations are uncommon in myeloma patients, and subacute polyradiculoneuropathy as the inaugural manifestations of solitary plasmacytoma of bone is exceedingly rare. We report the case of a 52-year-old man who was evaluated for a three-month history of flaccid tetraplegia with a gradually ascending onset and for a deterioration in general health. Electromyography findings were consistent with polyradiculoneuropathy. Laboratory tests showed a moderate amount of a monoclonal IgG-lambda antibody. Findings were normal from a radiographic bone survey and a radionuclide bone scan. Computed tomography of the pelvis disclosed a solitary osteolytic lesion in the right iliac crest, which was found upon biopsy to be a malignant plasmacytoma. Radiation therapy and chemotherapy were given. Subacute or chronic polyradiculoneuropathy as the inaugural manifestation of solitary plasmacytoma is exceedingly rare and should be distinguished from the sensorimotor polyneuropathy produced by plasma cell infiltration in some multiple myeloma patients. The polyradiculoneuropathy of solitary plasmacytoma can be likened to the neuropathies seen in some forms of multiple myeloma (sclerotic myeloma and POEMS syndrome). The pathophysiology of these neuropathies remains obscure. The case reported here suggests that patients with unexplained lasting polyradiculoneuropathy should be investigated for a plasma cell proliferation even if they have no serum monoclonal component. Because plasmacytomas are painless, imaging studies are needed for their diagnosis. The management of the neuropathy consists in treatment of the tumor.

Bone Neoplasms↗

PubMed1999

Linkage disequilibrium at the SCA2 locus.

Spinocerebellar ataxia type 2 (SCA2) is caused by the expansion of an unstable CAG repeat encoding a polyglutamine tract. Repeats with 32 to 200 CAGs are associated with the disease, whereas normal chromosomes contain 13 to 33 repeats. We tested 220 families of different geographical origins for the SCA2 mutation. Thirty three were positive (15%). Twenty three families with at least two affected subjects were tested for linkage disequilibium (LD) between the SCA2 mutation and three microsatellite markers, two of which (D12S1332-D12S1333) closely flanked the mutation; the other (D12S1672) was intragenic. Many different haplotypes were observed, indicating the occurrence of several ancestral mutations. However, the same haplotype, not observed in controls, was detected in the German, the Serbian, and some of the French families, suggesting a founder effect or recurrent mutations on an at risk haplotype.

Ataxins↗

PubMed1999

Rigid spine syndrome. Two case-reports.

UNLABELLED: Rigid spine syndrome is characterized by massive spinal rigidity, usually most marked in the cervical region. Stiffness of the peripheral joints is sometimes present. We report two cases. Patient 1 was a 12-year-old boy diagnosed at three years of age with Duchenne's muscular dystrophy because of delayed onset of walking. Contracture of the Achilles tendons, flexion contracture of the elbows, and loss of motion of the cervical spine were the main findings during the current evaluation. Radiographs of the affected joints were normal. An electrocardiogram showed an incomplete left bundle branch block. Muscle enzyme activities were moderately elevated. A myopathic pattern was seen on the electromyogram. A muscle biopsy showed muscle fiber atrophy with peri- and endomysial fibrosis. Patient 2 was a 39-year-old man with a five-year history of isolated rigidity of the cervical spine thought to be due to a spondylarthropathy. Extension was the only movement possible at the cervical spine. The peripheral joints showed no motion range limitation. Findings were normal from radiographs of the spine and sacroiliac joints, an erythrocyte sedimentation rate determination, an electromyogram, and muscle enzyme activity assays. A muscle biopsy showed muscle fiber atrophy with peri- and endomysial fibrosis. DISCUSSION: Rigid spine syndrome is rare in rheumatological practice and can simulate a number of other muscle and joint diseases. Peri- and endomysial fibrosis may be strongly suggestive, although nonpathognomonic. Involvement of the heart governs the prognosis.

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

The first de novo mutation of the connexin 32 gene associated with X linked Charcot-Marie-Tooth disease.

X linked Charcot-Marie-Tooth disease (CMTX) is a hereditary motor and sensory neuropathy caused by mutations in the connexin 32 gene (Cx32). Using the SSCP technique and direct sequencing of PCR amplified genomic DNA fragments of the Cx32 gene from a Moroccan patient and her relatives, we identified the first de novo mutation of the Cx32 gene, consisting of a deletion of a G residue at position 499 in the Cx32 open reading frame. This previously unreported mutation produces a frameshift at position 147 in the protein and introduces a premature stop codon (TAG) at nucleotide 643, which results in the production of a truncated Cx32 molecule. This mutation illustrates the risk of an erroneous diagnosis of autosomal recessive CMT, especially in populations where consanguineous unions are frequent, and its consequences for genetic counselling, which can be avoided by molecular analysis.

Adolescent↗

PubMed1997

Refinement of the locus for autosomal dominant cerebellar ataxia type II to chromosome 3p21.1-14.1.

We have previously mapped the gene for autosomal dominant cerebellar ataxia type II (ADCAII) to chromosome 3p12-p21.1 in a region of 33 cM by using four families of different geographic origin. In this study, we analysed the families with nine additional simple tandem repeat markers located in the ADCAII candidate region. An extensive clinical evaluation was also performed in the Belgian family CA-1 on two probably affected and seven at-risk individuals by means of ophthalmological examination and magnetic resonance imaging. Based on informative recombinants, we were able to reduce the ADCAII candidate region to the 12-cM region between D3S1300 and D3S1285. Furthermore, haplotype analysis among the families suggested that the most likely location of the ADCAII gene is within the 6.2-cM interval between D3S3698 and D3S1285. Because of the documented anticipation in ADCAII families, we also analysed family CA-1 with six polymorphic triplet repeat markers located on chromosome 3. None of these markers showed expanded alleles.

Cerebellar Ataxia↗

PubMed1997

[Cerebral infarction, pseudolupic syndrome and myxoma of the left atrium].

Left atrial myxomas are a rare stroke etiology (0.4%). They frequently present general symptoms such as fever, weight loss and an inflammatory syndrome, but the pseudolupic syndrome with cutaneous features and vasomotor symptoms is rarely described. We report the case of a 38-year old man who presented in March 1995 a stroke caused by a left atrial myxoma. There was also pseudolupic clinical and biological manifestations which disappeared after ablation of the myxoma. Cerebral angiography showed a small carotid aspect which evoked carotid dissection or carotid siphon occlusion. The authors discuss neurologic and pseudolupic manifestations of left atrial myxomas, and their physiopathologic mechanism.

Adult↗

PubMed1997

Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion.

The gene for spinocerebellar ataxia 7 (SCA7) has been mapped to chromosome 3p12-13. By positional cloning, we have identified a new gene of unknown function containing a CAG repeat that is expanded in SCA7 patients. On mutated alleles, CAG repeat size is highly variable, ranging from 38 to 130 repeats, whereas on normal alleles it ranges from 7 to 17 repeats. Gonadal instability in SCA7 is greater than that observed in any of the seven known neuro-degenerative diseases caused by translated CAG repeat expansions, and is markedly associated with paternal transmissions. SCA7 is the first such disorder in which the degenerative process also affects the retina.

Adult↗

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

Spinocerebellar ataxia 3 and Machado-Joseph disease: clinical, molecular, and neuropathological features.

Patients with spinocerebellar ataxia 3 (SCA3) and Machado-Joseph disease (MJD) carry an expanded CAG repeat in the MJD1 gene. One hundred twenty families of different geographic origin with autosomal dominant cerebellar ataxia (ADCA) type I were tested. Thirty-four families (126 patients) carried an expanded CAG repeat. The expanded and the normal allele did not overlap and the repeat was unstable during transmission, with variation in the size of the CAG length ranging from -8 to +5 and a mean expansion of 0.86 repeats without differences according to the parental sex. There was a combined effect of the number of CAG repeats of the expanded and normal allele on the age at onset, which accounted for 70% of its variability. The length of the CAG repeat influenced the frequency of clinical signs associated with cerebellar ataxia, such as abnormal tendon reflexes or decreased vibration sense, whereas the interindividual variation of supranuclear ophthalmoplegia, sphincter and swallowing difficulties, and amyotrophy was mostly determined by different disease durations. We compared the clinical profile of 91 SCA3/MJD patients with 51 SCA1 and 32 SCA2 patients. There were striking differences between the SCA3/MJD and SCA2 but not with SCA1 groups of patients. Despite their clinical similarities, distinct neuropathological features were observed in 2 SCA3/MJD and 2 SCA1 patients.

Adult↗

PubMed1996

Screening for proteins with polyglutamine expansions in autosomal dominant cerebellar ataxias.

Expansion of trinucleotide CAG repeats coding for polyglutamine has been implicated in five neurodegenerative disorders, including spinocerebellar ataxia (SCA) 1 and SCA3 or Machado-Joseph disease (SCA3/MJD), two forms of type I autosomal dominant cerebellar ataxias (ADCA). Using the 1C2 antibody which specifically recognizes large polyglutamine tracts, particularly those that are expanded, we recently reported the detection of proteins with pathological glutamine expansions in lymphoblasts from another form of ADCA type I, SCA2, as well as from patients presenting with the distinct phenotype of ADCA type II. We now have screened a large series of patients with ADCA or isolated cases with cerebellar ataxia, for the presence of proteins with polyglutamine expansions. A 150 kDa SCA2 protein was detected in 16 out of 40 families with ADCA type I. This corresponds to 24% of all ADCA type I families, which is much more frequent than SCA1 in this series of patients (13%). The signal intensity of the SCA2 protein was negatively correlated to age at onset, as expected for an expanded and unstable trinucleotide repeat mutation. The disease segregated with markers closely linked to the SCA2 locus in all identified SCA2 families. In addition, a specific 130 kDa protein, which segregated with the disease, was detected in lymphoblasts of patients from nine families with ADCA type II. It was also visualized in the cerebral cortex of one of the patients, demonstrating its translation in the nervous system. Finally, no new disease-related proteins containing expanded polyglutamine tracts could be detected in lymphoblasts from the remaining patients with ADCA or isolated cases with cerebellar ataxia.

Cerebellar Ataxia↗

PubMed1996

Intergenerational instability of the CAG repeat of the gene for Machado-Joseph disease (MJD1) is affected by the genotype of the normal chromosome: implications for the molecular mechanisms of the instability of the CAG repeat.

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder caused by unstable expansion of a CAG repeat in the MJD1 gene at 14q32.1. To identify elements affecting the intergenerational instability of the CAG repeat, we investigated whether the CGG/GGG polymorphism at the 3' end of the CAG repeat affects intergenerational instability of the CAG repeat. The [expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes were found to result in significantly greater instability of the CAG repeat compared to the [expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)nGGG]/[normal (CAG)n-GGG] haplotypes. Multiple stepwise logistic regression analysis revealed that the relative risk for a large intergenerational change in the number of CAG repeat units (< -2 or > 2) is 7.7-fold (95% CI: 2.5-23.9) higher in the case of paternal transmission than in that of maternal transmission and 7.4-fold (95% CI: 2.4-23.3) higher in the case of transmission from a parent with the [expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes than in that of transmission from a parent with the [expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)n-GGG]/[normal (CAG)n-GGG] haplotypes. The combination of paternal transmission and the [expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes resulted in a 75.2-fold (95% CI: 9.0-625.0) increase in the relative risk compared with that of maternal transmission and the [expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)n-GGG]/[normal (CAG)n-GGG] haplotypes. The results suggest that an inter-allelic interaction is involved in the intergenerational instability of the expanded CAG repeat.

Chromosomes, Human, Pair 14↗

PubMed1996

An expanded CAG repeat sequence in spinocerebellar ataxia type 7.

Expanded CAG repeat sequences have been identified in the coding region of genes mutated in several neurodegenerative disorders, including spinocerebellar ataxia type 1 and Machado-Joseph disease. In all disorders described to date the CAG expansion codes for an elongated polyglutamine chain. An increased polyglutamine chain size leads to a more severe disease, thus correlating with the genetic anticipation seen in repeat expansion disorders. Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant spinocerebellar ataxia with anticipation and a progressive degeneration of the cerebellar cortex. Using repeat expansion detection (RED), a method in which a thermostable ligase is used to detect repeat expansions directly from genomic DNA, we have analyzed 8 SCA7 families for the presence of CAG repeat expansions. RED products of 150-240 bp were found in all affected individuals and found to cosegregate with the disease (P < 0.000001, n = 66), indicating strongly that a CAG expansion is the cause of SCA7. On the basis of a previously established correlation between RED product sizes and actual repeat sizes in Machado-Joseph disease, we were able to estimate the average expansion size in SCA7 to be 64 CAG copies.

Chromosome Mapping↗

PubMed1996

[Cerebral vascular accidents due to hydatid embolisms. Apropos of 2 cases].

Hydatid cysts of the brain are very rare. Exceptionally, signs and symptoms are primarily those of acute cerebral ischaemia. Two cases of acute cerebral ischaemia are reported in a 21 year old and 40 year old women. A computed tomographic scan revealed a middle cerebral artery (MCA) infarct and an abrupt cutoff of the MCA at cerebral angiography. A few months later, a CT scan showed cysts in the territory of the infarct. Hydatid cysts were also found in multiple viscera, particularly in the heart. These two observations and some cases reported in the literature suggested that the myocardial cyst may have ruptured into the ventricular cavity, resulting in widespread intravascular dissemination of embryo and causing an acute cerebral infarction. The interest of these cases lies in the rarity of an acute cerebral ischaemia due to hydatid cyst embolism, and in the early diagnosis of cardiac cysts in young patients.

Adult↗

PubMed1995

The gene for autosomal dominant cerebellar ataxia with pigmentary macular dystrophy maps to chromosome 3p12-p21.1.

Autosomal dominant cerebellar ataxia with pigmentary macular dystrophy (ADCA type II) is a rare neurodegenerative disorder with marked anticipation. We have mapped the ADCA type II locus to chromosome 3 by linkage analysis in a genome-wide search and found no evidence for genetic heterogeneity among four families of different geographic origins. Haplotype reconstruction initially restricted the locus to the 33 cM interval flanked by D3S1300 and D3S1276 located at 3p12-p21.1. Combined multipoint analysis, using the Zmax-1 method, further reduced the candidate interval to an 8 cM region around D3S1285. Our results show that ADCA type II is a genetically homogenous disorder, independent of the heterogeneous group of type I cerebellar ataxias.

Adolescent↗

PubMed1994

Autosomal-dominant cerebellar ataxia with retinal degeneration (ADCA type II) is genetically different from ADCA type I.

Autosomal-dominant cerebellar ataxia (ADCA) type II is a neurodegenerative disorder presenting with cerebellar ataxia and retinal degeneration. We analyzed the clinical features of 21 patients with ADCA type II from 3 Moroccan and 2 French families. Mean age at onset was 17 years earlier in offspring than in their parents, compatible with anticipation. There was a suggestion of imprinting, with predominantly paternal transmission of early onset and severe forms of the affection. Candidate genes were tested in the family with the largest pedigree. The two known loci for ADCA type I (spinal cerebellar ataxia 1 and 2) were excluded, as were candidate loci, retinitis pigmentosa 1 locus (RP1) and the genes for rhodopsin and peripherin-rds, responsible for autosomal dominant retinitis pigmentosa. ADCA type II does not therefore result from an allelic mutation of the tested genes for ADCA type I or autosomal dominant retinitis pigmentosa.

Adolescent↗

PubMed1994

Middle cerebral artery occlusion due to hydatid cysts of myocardial and intraventricular cavity cardiac origin. Two cases.

BACKGROUND: Hemispheric strokes of hydatid origin are very rare. We describe two cases of middle cerebral artery occlusion by a cyst of cardiac origin. CASE DESCRIPTIONS: Cerebral angiography demonstrated occlusion of the initial segment of the middle cerebral artery. Myocardial and pericardial cysts were diagnosed by echography and pathological examination. Subsequent development of hydatid cysts within the necrotic area of the infarcted hemisphere suggests cerebral hydatid embolism of cardiac origin. CONCLUSIONS: In endemic areas, embolism of hydatid cysts should be considered in the diagnosis of stroke in young patients.

Adult↗