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O Dubourg

Publications and source records attributed to O Dubourg.

At least 19 recordsLinked to original sources
PubMed2006

Spine deformities in Charcot-Marie-Tooth 4C caused by SH3TC2 gene mutations.

BACKGROUND: Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of inherited peripheral motor and sensory neuropathies with several modes of inheritance: autosomal dominant, X-linked, and autosomal recessive (AR) CMT. A locus responsible for the demyelinating form of ARCMT was assigned to the 5q23-q33 region (CMT4C) by homozygosity mapping. Recently, 11 mutations were identified in the SH3TC2 (KIAA1985) gene in 12 families with demyelinating ARCMT from Turkish, Iranian, Greek, Italian, or German origin. OBJECTIVE: To identify mutations in the SH3TC2 gene. METHODS: The authors searched for SH3TC2 gene mutations in 10 consanguineous CMT families putatively linked to the CMT4C locus on the basis of haplotype segregation and linkage analysis. RESULTS: Ten families had mutations, eight of which were new and one, R954X, recurrent. Six of the 10 mutations were in exon 11. Onset occurred between ages 2 and 10. Scoliosis or kyphoscoliosis and foot deformities were found in almost all patients and were often inaugural. The median motor nerve conduction velocity values (</=34 m/s) were not correlated with disease duration. The functional disability score was </=3, indicating that the patients could walk without help. Unexpectedly, typical giant axons were observed on biopsies from a large Algerian family. CONCLUSIONS: Charcot-Marie-Tooth type 4C (CMT4C) is less severe than other autosomal recessive (AR) CMT. Intrafamilial variability is important, making phenotype-genotype correlations difficult, but spine deformities are clearly a hallmark of CMT4C. In the presence of scoliosis, a neurologic examination is recommended. Giant axons on biopsies are also suggestive of CMT4C. For genetic analysis, the R954X mutation should be looked for before systematic sequencing of exon 11.

Charcot-Marie-Tooth Disease↗
PubMed2006

The G526R glycyl-tRNA synthetase gene mutation in distal hereditary motor neuropathy type V.

BACKGROUND: Distal hereditary motor neuropathy (dHMN) or distal spinal muscular atrophy (dSMA) is a heterogeneous group of disorders characterized almost exclusively by degeneration of motor nerve fibers, predominantly in the distal part of the limbs. One subtype, dHMN type V (dHMN-V), is transmitted by autosomal dominant inheritance and predominantly involves the hands. It is allelic with Charcot-Marie-Tooth disease 2D (CMT2D), in which a similar phenotype is associated with sensory signs. Missense mutations in the glycyl-tRNA synthetase (GARS) gene have been recently reported in families with either dHMN-V, CMT2D, or both. METHODS: The authors searched for GARS mutations in eight dHMN-V families. RESULTS: The authors found the G526R missense mutation in three families (16 patients) of Algerian Sephardic Jewish origin. All patients shared a common disease haplotype, suggestive of a founder effect. The clinical phenotype consists of a slowly progressive, purely motor distal neuropathy. It starts in the hands in most patients, but also in both distal upper and lower limbs or in distal lower limbs alone. The age at onset in symptomatic individuals was between the second to fourth decades, but four mutation carriers were still asymptomatic, two of whom were already age 49 years. Electrophysiology showed that the motor fibers of the median nerve were the most affected in upper limbs. Sensory nerve action potentials were normal. CONCLUSIONS: The age at onset of patients with the G526R mutation in the GARS gene varied widely, but the clinical and electrophysiologic presentation was uniform and progressed slowly. Glycyl-tRNA synthetase mutations are a frequent cause of familial distal hereditary motor neuropathy type V but, because of the reduced penetrance of the disease, could also account for isolated cases.

Age of Onset↗
PubMed2006

Autosomal-recessive forms of demyelinating Charcot-Marie-Tooth disease.

Autosomal-recessive forms of Charcot-Marie-Tooth (ARCMT) account for less than 10% of the families in the European CMT population but are more frequent in the Mediterranean basin and the Middle East because of more widespread consanguinity. Until now, demyelinating ARCMT was more extensively studied at the genetic level than the axonal form. Since 1999, the number of localized or identified genes responsible for demyelinating ARCMT has greatly increased. Eight genes, EGR2, GDAP1, KIAA1985, MTMR2, MTMR13, NDRG1, PRX, and CTDP1, have been identified and two new loci mapped to chromosomes 10q23 and 12p11-q13. In this review, we will focus on the particular clinical and/or neuropathological features of the phenotype caused by mutations in each of these genes, which might guide molecular diagnosis.

Cataract↗
PubMed2006

[Type B natriuretic peptide (BNP) versus n-terminal type B natriuretic propeptide in the diagnosis of cardiac failure in the elderly over 75 population].

Type B natriuretic peptide (BNP) versus n-terminal type B natriuretic propeptide in the diagnosis of cardiac failure in the elderly over 75 population The value of BNP is well established in the diagnosis of cardiac failure in cases of dyspnoea in the emergency room in young and, more and more, in elderly subjects. However, there are few studies comparing the diagnostic value of BNP and of the n-terminal pro-BNP in patients over 75 years of age. The aim of this study was to compare the diagnostic value of BNP and NT-pro BNP in dyspnoea of the elderly patient. One hundred and three consecutive patients over 75 years of age admitted to the emergency unit for dyspnoea were included. A blood sample for measuring the BNP (Biosite) and the NT-proBNP (Roche Diagnostic) was taken in the admission unit in addition to the standard blood workup. The final reference diagnosis was established by two independent cardiologists. Of the 103 patients, 61 were women and the average age was 84.9 +/- 6.2 years. The final diagnosis was cardiac failure in 49 patients (48%), pulmonary embolism in 6 patients, an acute exacerbation of chronic obstructive airways disease in 36 patients and an acute bronchitis in 30 patients. In 9 cases, the dyspnoea was considered to result from mixed cardiac and pulmonary disease. Renal function was assessed by calculating the creatinine clearance by Cockcroft and Gault's formula. The average value of the creatinine clearance was 41.7 +/- 16.4 ml/min indicating that mild renal failure was relatively common. The diagnostic value, assessed by the area under the ROC curve, was similar for the BNP (0.79; CI: 0.70-0.88) and NT-proBNP (0.80; CI: 0.71-0.89). A BNP value of 300 pg/ml had the same sensitivity and specificity as an NT-proBNP of less than 1 500 pg/ml. A BNP of less than 200 pg/ml and an NT-proBNP of less than 1 000 pg/ml had excellent negative predictive values for excluding the diagnosis of cardiac failure. The authors conclude that the BNP and NT-proBNP are useful for the diagnosis of cardiac failure in acute dyspnoea of the elderly and seem to have a comparable diagnostic value.

Aged↗
PubMed2006

[The role of spiral computerized tomography in the diagnosis of pulmonary embolism].

The diagnostic strategy of pulmonary embolism has changed in the last few years with the use of the pulmonary spiral angio-scan. It has become the investigation of first intention for the positive diagnosis of pulmonary embolism. Its limitations are known, essentially the difficulties in visualisation of distal pulmonary embolism. However, the introduction of new 64-slice scanners has considerably improved the resolution. The indications of the spiral angioscanner have recently increased with the study of pulmonary artery vascularisation and the calculation of Qanadli's obstruction index, the study of the peripheral venous system and the evaluation of right ventricular dysfunction by the calculation of the ratio of surfaces (or diameters) of RV/LV.

Arterial Occlusive Diseases↗
PubMed2006

[Diagnostic value of a two-dimensional echocardiographic score for left ventricular hypertrophy validated by the Imatron CT scan in familial hypertrophic cardiomyopathy].

The aim of this study was to validate a two-dimensional echocardiographic score for left ventricular hypertrophy in familial hypertrophic cardiomyopathy (HCM) by fast CT scan and to study the diagnostic value by an indexed threshold value in affected and genotyped families in comparison with the classical diagnostic method of maximal wall thickness (E max). The study was performed successively in two patient groups with HCM. The echo/CT scan population comprised 26 patients. They underwent echocardiography and Imatron CT scanning. The E max and 2D echo score (sum of the thickness of 4 segments) were measured by echocardiography and compared to the left ventricular mass obtained by the CT method. The 2D echo score was closely correlated to the CT left ventricular mass (r = 0.85) with a higher correlation coefficient than the E max (r = 0.78). The echo/generic population comprised 109 genotyped adults with an identified mutation. The E max and 2D echo score were measured. The genotype was the reference for diagnosis. A theoretical value of the 2D echo score was determined in healthy individuals by a multiple linear regression model of ages, sex and body surface area. A threshold value for abnormality was established after analysis of the ROC. The sensitivity and specificity were 63% and 100% respectively for E max and 73% and 96% respectively for the indexed 2D echo score. The improvement in sensitivity was marked in young adults (< 50 years) with 69% for the indexed 2D echo score versus 54% for E max, p < 0.04. The authors conclude that the indexed 2D score has been validated as an index of hypertrophy by the Imatron CT and has a better diagnostic value than E max, especially in young adults. This echocardiographic criterion could be proposed as an alternative diagnostic sign for screening families.

Adult↗
PubMed2005

[Intramuscular vascular malformations as a differential diagnosis of focal myositis].

INTRODUCTION: Focal myositis constitutes an original and rare pathological entity, characterized by a localized inflammation within skeletal muscle, presenting as a soft tissue painful tumefaction. Diagnosis requires histological confirmation because of its non-specific clinical feature and the numerous differential diagnoses. EXEGESIS: We report a 27 year-old man who presented with suggestive symptoms of focal myositis. MR imaging and echography were compatible with this diagnosis but also demonstrated the existence of a vascular component within the tumefaction. The diagnosis of a benign vascular malformation with intramuscular development was made by a surgically guided biopsy. CONCLUSION: Vascular malformations are histologically heterogeneous with extremely variable clinical expressions. When they develop within skeletal muscle, they may mimic focal myositis. Hence, their diagnosis has to be evoked before performing muscle biopsy, because of the potential hemorrhagic risk.

Adult↗
PubMed2005

[Apical left ventricular aneurysm without atrio-ventricular block due to a lamin A/C gene mutation].

UNLABELLED: Mutations in LMNA gene encoding two ubiquitously expressed nuclear proteins, lamins A and C, give rise to up to 7 different pathologies affecting specific tissues. Three of these disorders affect cardiac and/or skeletal muscles with atrio-ventricular conduction disturbances, dilated cardiomyopathy and sudden cardiac death as common features. RESULTS: A new LMNA mutation (1621C>T, R541C) was found in two members of a French family with a history of ventricular rhythm disturbances and an uncommon form of systolic left ventricle dysfunction. The two patients: the proband and his daughter, were affected and exhibited an atypical form of dilated cardiomyopathy with an unexplained left ventricle aneurysm revealed by ventricular rhythm disturbances without atrio-ventricular block. CONCLUSION: This finding reinforces the highly variable phenotypic expression of LMNA mutation and emphasizes the fact that LMNA mutations can be associated with different cardiac phenotypes.

Adult↗
PubMed2004

Coincidence of two genetic forms of Charcot-Marie-Tooth disease in a single family.

The authors report a family in which two affected first cousins had a severe demyelinating Charcot-Marie-Tooth disease (CMT) phenotype. One had related parents, and there were no other affected relatives, suggesting an autosomal recessive mode of inheritance. Molecular studies showed that a de novo duplication in 17p11.2 and a second mutation in MTMR2 were present.

Adolescent↗
PubMed2004

[Skeletal muscle efficiency in heart failure].

Heart failure is associated with modifications of skeletal muscle cells, which could participate in the exercise limitation of the patients. However, the mechanical efficiency of the skeletal muscle has not been fully evaluated in these patients. We therefore measured VO2 during prolonged exercise (15 min) at constant load to obtain stable conditions. Load was chosen after maximal stress test as 35% and 65% of load at anaerobic threshold. VO2 during assisted cycling was subtracted from that during constant load to evaluate the relationship between VO2 and Watt. Twenty CHF patients (peak VO2 17.6 ml/kg/min, LVEF <35%) have been compared to 11 controls (peak VO2 40.2 ml/ml/kg). VO2 was similar in the two groups at rest and during assisted cycling. Ventilation on contrary was higher in CHF patients. The relationship between VO2 and Watt was similar in the two populations, indicating that skeletal muscle mechanical efficiency was not altered in CHF patients. In conclusion, histological modifications present in skeletal muscle of CHF patients do not translate into altered skeletal muscle efficiency.

Adult↗
PubMed2004

[Acute lithium intoxication. Apropos of a case].

Lithium salts are used in psychiatry for the treatment of bipolar depression. An overdose is potentially serious, sometimes fatal, and the clinical signs are variable. The authors report the case of a 70 year old man. He had a recent history of a transient ischaemic attack and was admitted to the coronary care unit for bradycardia at 35-40 BPM and episodes of sino-atrial block with a clinical presentation suggestive of a stroke. The diagnosis of lithium intoxication was made accounting for the present hospital admission and for the previous neurological event which had been diagnosed as a transient ischaemic attack. The difficulty of diagnosis of this condition is discussed.

Aged↗
PubMed2004

[Echographic calculation of left ventricular mass in TM mode].

UNLABELLED: TM sections of the left ventricle (LV) have only been validated in fundamental (F) imaging. We were interested in evaluating the repercussions of new imaging techniques, harmonic (H) and colour tissue Doppler (CTD), on the TM measurement of left ventricular mass (LVM), the reference imaging being F imaging. METHOD: We performed a prospective study, including 26 patients with a valid TM section. The LV and LVM parameters in F, H and CTD mode according to the Penn and ASE conventions as well as the inter-observer reproducibility were studied. RESULTS: The correlations for the LVM measurements between F and H, and between F and CTD were high whichever convention was used (r>0.95, p<0.0001). For each observer, the LVM in H and in CTD was always greater than the LVM in F with both conventions (p<0.02). A false diagnosis of LV hypertrophy was made in 27% of patients in H and in 15% of patients in CTD. The best inter-observer reproducibility was obtained in H: the average inter-observer difference (gr.) was 23+/-15 for H, 32+/-19 for F and 59+/-18 for CTD. CONCLUSION: H and CTD imaging entail an overestimation of LVM, essentially by overestimation of the parietal thickness of the LV. The inter-observer reproducibility was excellent in H and poor in CTD. The use of the harmonic mode for LVM calculation must be validated using new formulae.

Adult↗
PubMed2003

Accuracy of European diagnostic criteria for familial hypertrophic cardiomyopathy in a genotyped population.

BACKGROUND: Since the sensitivity of conventional diagnostic criteria for familial hypertrophic cardiomyopathy (HCM) is low, new diagnostic criteria were proposed by a European collaboration. However, their diagnostic value remains unknown. The aim of the study was to evaluate the accuracy of these new criteria, using the genetic status as the criterion of reference. METHODS: We studied 109 genotyped adults (54 genetically affected, 55 unaffected) from 7 families (mutations in 3 genes). Major European echographic criteria were a maximal wall thickness >or=13 mm or >or=15 mm according to the segment involved, or the presence of SAM. Major European ECG criteria were abnormal Q waves, left ventricular hypertrophy, or marked ST-T changes. Combined major/minor European criteria were also evaluated. RESULTS: Sensitivity and specificity of major European criteria (72 and 92%, respectively) were similar to those of major conventional criteria (70 and 94%) and were not improved by combined major/minor European criteria (72 and 90%). When all the minor European criteria were considered, sensitivity increased to 87% but specificity dramatically decreased to 51%. However, one of these minor ECG criteria, deep S V2, was of interest and when added to major European criteria, sensitivity increased to 76% and specificity remained good (90%). CONCLUSIONS: The diagnostic value of new European criteria for HCM was evaluated for the first time. We found that it was not different from that of conventional criteria, with a good specificity but a low sensitivity. Additional criteria should be studied to improve the early identification of HCM.

Adult↗
PubMed2003

Autonomic and respiratory dysfunction in Charcot-Marie-Tooth disease due to Thr124Met mutation in the myelin protein zero gene.

OBJECTIVE: To report the clinical and electrophysiological characteristics of a family presenting Charcot-Marie-Tooth disease (CMT) associated with autonomic nervous system disturbances. METHODS: We studied nerve conduction values, postural adaptation, sympathetic skin reflex, the variation in heart rate by the Valsalva ratio and pupillometry in 7 members of a French family in which CMT due to a Thr124Met mutation in the myelin protein zero (MPZ) gene was diagnosed. RESULTS: Clinical and laboratory evidence of autonomic nervous system disturbances were found in the affected individuals. The clinical phenotype was characterized by sensorimotor peripheral neuropathy, defined as axonal type by electrophysiological studies, and was associated with severe pain, bladder dysfunction, sudorimotor disturbances and abolished pupillary reflex to light. Moreover, two patients had severe restrictive respiratory insufficiency requiring noninvasive mechanical ventilation. CONCLUSIONS: Our study demonstrates that autonomic disturbances may be one of the major clinical signs associated with CMT secondary to MPZ gene mutation in codon 124. Testing of pupillary reflex allows the discrimination of affected and unaffected subjects in our family. However, involvement of the autonomic nervous system in this type of neuropathy is unclear and further studies are required to elucidate the role of the MPZ gene in the autonomic nervous system.

Adult↗
PubMed2003

Clinical significance of tolerant strains of streptococci in adults with infective endocarditis.

OBJECTIVES: To compare the characteristics of patients with endocarditis due to tolerant and non-tolerant Streptococcus strains. PATIENTS AND METHODS: A retrospective nine-year study was conducted in a single tertiary-care hospital. The study included 24 cases of streptococcal endocarditis with known beta-lactam minimal inhibitory and bactericidal concentrations. RESULTS: Ten of the 24 patients concerned were infected with tolerant streptococcal strains, and 14 with non-tolerant strains. Bacterial tolerance was not associated with higher mortality or increased frequency of surgery. Fewer patients infected with tolerant than non-tolerant strains had serum bactericidal titers reaching success-predictive levels, and more of these experienced failure of initial antibiotic treatment and needed longer treatment. CONCLUSIONS: The results of this study strongly suggest that penicillin tolerance of the streptococci responsible for endocarditis has a clinical impact. Consequently, pending a larger prospective study addressing the problem of tolerance, it is clinically relevant to determine the minimal inhibitory and bactericidal penicillin concentrations for all streptococcal isolates causing endocarditis.

Adult↗
PubMed2003

Variability of disease progression in a family with autosomal recessive CMT associated with a S194X and new R310Q mutation in the GDAP1 gene.

Charcot-Marie-Tooth (CMT) with autosomal recessive (AR) inheritance is a heterogeneous group of inherited motor and sensory neuropathies. Six genes and five additional loci have been identified that are responsible for either demyelinating or axonal forms of the disease. The gene encoding the ganglioside-induced-differentiation-associated protein 1 (GDAP1) has been associated with both demyelinating and axonal phenotypes. We report a detailed clinical, electrophysiological, and genetic study of two siblings from a Moroccan ARCMT family who are compound heterozygotes for the already described S194X and a new R310Q mutation in the GDAP1 gene. The electrophysiological data are compatible with an axonal form of the disease. The phenotype included hoarse voice and paralysis of the diaphragm. This study shows the variability of the phenotype associated with mutations in GDAP1 gene in terms of associated signs and severity.

Adult↗