Khadilkar S.V.,Sir Jj Group Of Hospitals |
Mansukhani K.A.,Bombay Hospital |
Sternberg D.,Federation de Genetique
Muscle and Nerve | Year: 2010
Pyridostigmine relieved episodic weakness in a family with paramyotonia congenita resulting from the R1448C mutation in the sodium channel gene. The transmission was autosomal dominant and the patients had paradoxical myotonia and exercise-induced weakness. On electrophysiological studies there were myotonic potentials, and there was progressive reduction of compound muscle action potential (CMAP) amplitudes after short exercise associated with clinical weakness. Pyridostigmine in doses of 60 mg three times daily abolished the drop in the postexercise CMAP amplitude and reduced the amplitude decrement to slow rate repetitive stimulation, but there continued to be a drop in amplitude on exposure to cold. The decline of the CMAP amplitude on exposure to cold was controlled by treatment with phenytoin. The clinical and electrophysiological features are discussed in relation to therapy with pyridostigmine and phenytoin. © 2009 Wiley Periodicals, Inc.
Goizet C.,Bordeaux University Hospital Center |
Goizet C.,University of Bordeaux Segalen |
Anheim M.,Federation de Genetique |
Anheim M.,University of Paris Descartes |
And 4 more authors.
Pratique Neurologique - FMC | Year: 2012
Autosomal dominant cerebellar ataxias (ADCA) constitute a heterogeneous group of rare neurodegenerative disorders. In clinical practice, sporadic cases of cerebellar ataxia are much more frequent. The progressive identification of genes implicated in ADCA has confirmed the wild genetic heterogeneity of these conditions. To date, at least 30 loci and 20 genes have been identified. The phenotype is generally not restricted to cerebellar signs, associating other neurological or non-neurological features. The most frequent forms of ADCA in France (spinal cerebellar ataxia [SCA]1, 2, 3, 6, and 7), as well as SCA17 and dentatorubro-pallido-luysian atrophy (DRPLA) are caused by CAG repeat expansions in coding regions leading to polyglutamin repeats in the corresponding proteins. The repeat size influences age at onset, progression of the disease, and clinical differences among patients. The CAG expansions also provide a strong molecular explanation for the phenomenon of anticipation. All other ADCA are much rarer and caused either by non-coding repeat expansions, conventional mutations or large rearrangements in genes with different functions. © 2011 Elsevier Masson SAS. All rights reserved.
Vincent M.,Nantes University Hospital Center |
Vincent M.,Montpellier University |
Genevieve D.,Montpellier University |
Ostertag A.,French Institute of Health and Medical Research |
And 53 more authors.
Genetics in Medicine | Year: 2016
Purpose:Treacher Collins/Franceschetti syndrome (TCS; OMIM 154500) is a disorder of craniofacial development belonging to the heterogeneous group of mandibulofacial dysostoses. TCS is classically characterized by bilateral mandibular and malar hypoplasia, downward-slanting palpebral fissures, and microtia. To date, three genes have been identified in TCS:,TCOF1, POLR1D, and POLR1C.Methods:We report a clinical and extensive molecular study, including TCOF1, POLR1D, POLR1C, and EFTUD2 genes, in a series of 146 patients with TCS. Phenotype-genotype correlations were investigated for 19 clinical features, between TCOF1 and POLR1D, and the type of mutation or its localization in the TCOF1 gene.Results:We identified 92/146 patients (63%) with a molecular anomaly within TCOF1, 9/146 (6%) within POLR1D, and none within POLR1C. Among the atypical negative patients (with intellectual disability and/or microcephaly), we identified four patients carrying a mutation in EFTUD2 and two patients with 5q32 deletion encompassing TCOF1 and CAMK2A in particular. Congenital cardiac defects occurred more frequently among patients with TCOF1 mutation (7/92, 8%) than reported in the literature.Conclusion:Even though TCOF1 and POLR1D were associated with extreme clinical variability, we found no phenotype-genotype correlation. In cases with a typical phenotype of TCS, 6/146 (4%) remained with an unidentified molecular defect. © 2016 American College of Medical Genetics and Genomics.
Meneret A.,French Institute of Health and Medical Research |
Meneret A.,University Pierre and Marie Curie |
Grabli D.,French Institute of Health and Medical Research |
Grabli D.,University Pierre and Marie Curie |
And 25 more authors.
Neurology | Year: 2012
Objective: Paroxysmal kinesigenic dyskinesia (PKD) is a rare disorder characterized by recurrent attacks of hyperkinetic movements. PKD can be isolated or associated with benign infantile seizures as part of the infantile convulsions with choreoathetosis (ICCA) syndrome. Mutations in the PRRT2 gene were recently identified in patients with PKD and ICCA. We studied the prevalence of PRRT2 mutations and characteristics of the patients in a European population of patients with PKD and ICCA. Methods: Patients were recruited through the 1996-2011 database of our DNA bank, to which physicians refer DNA with a putative diagnosis and clinical information. Two movement disorders experts reviewed the information on patients with a putative diagnosis of PKD. Patients who fulfilled the criteria for PKD and ICCA were included. The PRRT2 coding sequence was analyzed by direct sequencing. Results: Among 42 index cases of unrelated families referred with a putative diagnosis of PKD, a total of 34 patients, including 32 with isolated PKD and 2 with ICCA, were selected for genetic analysis. Mutations introducing premature termination codons were identified in 22 of 34 patients including 13 of 14 families and 9 of 20 patients with sporadic cases. The previously described c.649dupC/pArg217ProfsX8 and c.629dupC/pAla211SerfsX14 were present, respectively, in 17 patients and 1 patient; we also report 3 novel mutations: c.649delC/pArg217GlufsX12 in 2 patients, and c.562C>T/pGln188X and c.649C>T/pArg217X, each in 1 patient. The group with mutations was characterized by a younger age at onset (9 years) compared with the patients without mutations (15 years; p < 0.01). Conclusion: Mutations in PRRT2 are a major cause of PKD in familial and sporadic cases in the European population. Copyright © 2012 by AAN Enterprises, Inc.
Doco-Fenzy M.,Service de Genetique |
Leroy C.,Service de Genetique |
Schneider A.,UniversiteMontpellier 1 |
Petit F.,Lille University Hospital Center |
And 20 more authors.
European Journal of Human Genetics | Year: 2014
Obesity is a common but highly, clinically, and genetically heterogeneous disease. Deletion of the terminal region of the short arm of chromosome 2 is rare and has been reported in about 13 patients in the literature often associated with a Prader-Willi-like phenotype. We report on five unrelated patients with 2p25 deletion of paternal origin presenting with early-onset obesity, hyperphagia, intellectual deficiency, and behavioural difficulties. Among these patients, three had de novo pure 2pter deletions, one presented with a paternal derivative der(2)t(2;15)(p25.3;q26) with deletion in the 2pter region and the last patient presented with an interstitial 2p25 deletion. The size of the deletions was characterized by SNP array or array-CGH and was confirmed by fluorescence in situ hybridization (FISH) studies. Four patients shared a 2p25.3 deletion with a minimal critical region estimated at 1.97 Mb and encompassing seven genes, namely SH3HYL1, ACP1, TMEMI8, SNTG2, TPO, PXDN, and MYT1L genes. The fifth patient had a smaller interstitial deletion encompassing the TPO, PXDN, and MYT1L genes. Paternal origin of the deletion was determined by genotyping using microsatellite markers. Analysis of the genes encompassed in the deleted region led us to speculate that the ACP1, TMEM18, and/or MYT1L genes might be involved in early-onset obesity. In addition, intellectual deficiency and behavioural troubles can be explained by the heterozygous loss of the SNTG2 and MYT1L genes. Finally, we discuss the parent-of-origin of the deletion. © 2014 Macmillan Publishers Limited.