European Journal of NeurologyVolume 25, Issue 12 p. e123-e124 Letter to the Editor MYOD1 involvement in myopathy F. Lopes, F. Lopes Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Quebec, CanadaSearch for more papers by this authorM. Miguet, M. Miguet CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada CHU de Strasbourg, Pôle de biologie, Alsace, FranceSearch for more papers by this authorB. E. Mucha, B. E. Mucha CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Quebec, CanadaSearch for more papers by this authorJ. Gauthier, J. Gauthier CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada Medical Biological Unit, Molecular Diagnostic Laboratory, Sainte-Justine University Hospital Center, Montreal, QC, CanadaSearch for more papers by this authorV. Saillour, V. Saillour CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada Centre de génomique clinique pédiatrique intégré, Génome Québec et CHU Sainte-Justine, Montreal, QC, CanadaSearch for more papers by this authorC.-T. É. Nguyen, C.-T. É. Nguyen CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada Department of Pediatrics, Sainte-Justine University Hospital Center, Montreal, QC, CanadaSearch for more papers by this authorM. Vanasse, M. Vanasse CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada Department of Pediatrics, Sainte-Justine University Hospital Center, Montreal, QC, CanadaPosthumously.Search for more papers by this authorB. Ellezam, B. Ellezam CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada Department of Pathology, CHU Sainte-Justine, Montreal, QC, CanadaSearch for more papers by this authorJ. L. Michaud, J. L. Michaud CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada Department of Pediatrics, Sainte-Justine University Hospital Center, Montreal, QC, CanadaSearch for more papers by this authorJ.-F. Soucy, J.-F. Soucy CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada Medical Biological Unit, Molecular Diagnostic Laboratory, Sainte-Justine University Hospital Center, Montreal, QC, CanadaSearch for more papers by this authorP. M. Campeau, Corresponding Author P. M. Campeau p.campeau@umontreal.ca CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada Department of Pediatrics, Sainte-Justine University Hospital Center, Montreal, QC, CanadaCorrespondence: P. M. Campeau, CHU Sainte-Justine, 3175, Côte-Ste-Catherine, Montreal, H3T 1C5 QC, Canada (tel.: +1 514 345 4931, ext 7146; fax: +1 514 345 4766; e-mail: p.campeau@umontreal.ca).Search for more papers by this author F. Lopes, F. Lopes Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Quebec, CanadaSearch for more papers by this authorM. Miguet, M. Miguet CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada CHU de Strasbourg, Pôle de biologie, Alsace, FranceSearch for more papers by this authorB. E. Mucha, B. E. Mucha CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Quebec, CanadaSearch for more papers by this authorJ. Gauthier, J. Gauthier CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada Medical Biological Unit, Molecular Diagnostic Laboratory, Sainte-Justine University Hospital Center, Montreal, QC, CanadaSearch for more papers by this authorV. Saillour, V. Saillour CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada Centre de génomique clinique pédiatrique intégré, Génome Québec et CHU Sainte-Justine, Montreal, QC, CanadaSearch for more papers by this authorC.-T. É. Nguyen, C.-T. É. Nguyen CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada Department of Pediatrics, Sainte-Justine University Hospital Center, Montreal, QC, CanadaSearch for more papers by this authorM. Vanasse, M. Vanasse CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada Department of Pediatrics, Sainte-Justine University Hospital Center, Montreal, QC, CanadaPosthumously.Search for more papers by this authorB. Ellezam, B. Ellezam CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada Department of Pathology, CHU Sainte-Justine, Montreal, QC, CanadaSearch for more papers by this authorJ. L. Michaud, J. L. Michaud CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada Department of Pediatrics, Sainte-Justine University Hospital Center, Montreal, QC, CanadaSearch for more papers by this authorJ.-F. Soucy, J.-F. Soucy CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada Medical Biological Unit, Molecular Diagnostic Laboratory, Sainte-Justine University Hospital Center, Montreal, QC, CanadaSearch for more papers by this authorP. M. Campeau, Corresponding Author P. M. Campeau p.campeau@umontreal.ca CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada Department of Pediatrics, Sainte-Justine University Hospital Center, Montreal, QC, CanadaCorrespondence: P. M. Campeau, CHU Sainte-Justine, 3175, Côte-Ste-Catherine, Montreal, H3T 1C5 QC, Canada (tel.: +1 514 345 4931, ext 7146; fax: +1 514 345 4766; e-mail: p.campeau@umontreal.ca).Search for more papers by this author First published: 07 November 2018 https://doi.org/10.1111/ene.13782Citations: 7 Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Supporting Information Filename Description ene13782-sup-0001-Suppinfo.docxWord document, 1.1 MB Appendix S1. Myogenic Differentiation 1 involvement in myopathy. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume25, Issue12December 2018Pages e123-e124 RelatedInformation

Taurine and B-alanine uptake in cultured skin fibroblasts proceeds through at least two distinct amino acid transport systems. The predominant Bamino acid uptake system which we refer to as the "Beta" system, incorporates taurine in a proportion of 95%, B-alanine in a proportion of 80% and does not incorporate f}-amino-isobutyric acid. A second transport system for B-alanine seems to be operative in cultured skin fibroblasts and

IntroductionHeart involvement in Friedreich's ataxia (FRDA) is present in 63% of patients at diagnosis. The most common echocardiographic abnormality is a progressive hypertrophic cardiomyopathy. The use of antioxidants such as idebenone has shown promising results in improving cardiac hypertrophy parameters at low to intermediate dose. The long term cardiac effects of a higher dose of idebenone have not been studied. The objective of the study is to evaluate the effects of high dose idebenone (Hi-IDB) on cardiac function and myocardial hypertrophy in paediatric FDRA patients and to compare these parameters with low dose of idebenone (Lo-IDB).MethodsIn this prospective, comparative, non-controlled open trial we compare HI-IDB to Lo-IDB 12-month therapeutic regimens. A cohort of 9 children with genetic diagnosis of FDRA received the following Hi-IDB (450mg/day if 45kg for 6 months, increased to 1250mg/day thereafter), and were compared to a cohort of 11 patients treated with Lo-IDB (5mg/kg/day). Cardiac evaluation was performed before therapy and every three months for a total of 12 months. Clinical and echocardiographic data -systolic and diastolic function, left ventricular wall thickness and mass index (LVMi)- were recorded.ResultsPatients were 13.6 ± 2.4 v.s. 11.9 ± 4.7 years old at enrolment (Lo-IDB v.s. Hi-IDB; P = 0.54). Baseline LVMi were comparable between groups (62.5 ± 25.0 v.s. 58.4 ± 39.4 g/m2; P = 0.323). Significant LVMi reduction from baseline was observed in Lo-IDB after 6, 9, and 12 months (P = 0.02, 0.007, & 0.002). In the Hi-IDB, 3 patients discontinued therapy after 9 months, with statistically significant LVMi reduction compared to baseline at 9 and 12 months (P = 0.032 & 0.039) all subjects included. Comparison between Lo-IDB and Hi-IDB for LVMi reduction was not statistically significant at 9 or 12 months (P = 0.43 & 0.16). (figure) . Systolic function parameters where within normal range in all patients, with no significant differences between baseline and last follow-up in either group. There were no major significant changes in diastolic function parameters, with the exception of improved mitral deceleration time with Hi-IDB between baseline and last follow-up (138.8 ± 21.3 v.s. 162.6 ± 20.6 cm/sec; P = 0.029).ConclusionThere are comparable effects of HI-IDB and Lo-IDB in terms of reduction of left ventricular hypertrophy parameters. Both therapeutic regimens seem to preserve systolic cardiac function, with the advantage of Hi-IDB to improve diastolic function. Remote effect on reducing the risk of dilated cardiomyopathy and subsequent death needs to be studied.CHU-Sainte Justine Foundation IntroductionHeart involvement in Friedreich's ataxia (FRDA) is present in 63% of patients at diagnosis. The most common echocardiographic abnormality is a progressive hypertrophic cardiomyopathy. The use of antioxidants such as idebenone has shown promising results in improving cardiac hypertrophy parameters at low to intermediate dose. The long term cardiac effects of a higher dose of idebenone have not been studied. The objective of the study is to evaluate the effects of high dose idebenone (Hi-IDB) on cardiac function and myocardial hypertrophy in paediatric FDRA patients and to compare these parameters with low dose of idebenone (Lo-IDB).

Recessive ataxias are a heterogeneous group of diseases. We identified a group of 23 French-Canadian cases belonging to 17 families affected by an autosomal recessive spastic ataxia associated with frequent white matter changes. The fact that 59% of these families have a genealogical relationship to the Portneuf County of Quebec suggests that this is a new form of ataxia with a regional founder effect. All cases present with cerebellar ataxia and spasticity. There is great intrafamilial and interfamilial variability, as illustrated by the spectrum of age of diagnosis (range: 2-59 years, mean: 15.0) and the presence of white matter changes on MRI in 52.4% of cases. The more severe cases have spasticity from birth, scoliosis, dystonia and cognitive impairment and were considered cases of cerebral palsy. Brain MRI constantly shows cerebellar atrophy, which in some cases may be associated with cortical atrophy, leucoencephalopathy and corpus callosum thinning. A genome wide scan uncovered linkage of three families to marker D2S2321 localized on chromosome 2q33-34. Linkage analysis confirmed that all families are linked to the same region [multipoint log of the odds (LOD) score of 5.95]. Haplotype analysis and allele sharing suggest that one common mutation may account for 97% of carrier chromosomes in Quebec. The uncovering of the mutated gene may point to a common pathway for pyramidal and cerebellar degeneration as both are often observed in recessive ataxias and complicated paraplegias.

Congenital muscular dystrophies (CMDS) are a heterogeneous group of disorders. A growing number of CMDS have been found to be associated with joint hyperlaxity. We recruited 14 French-Canadian cases belonging to 11 families affected by a novel autosomal recessive congenital muscular dystrophy with hyperlaxity (CMDH). All cases come from the southwestern part of Quebec, suggesting a new French-Canadian founder effect. All patients present muscle weakness, proximal contractures coexisting with distal joint hyperlaxity. Pathological and genetic studies have excluded that mutations in the three genes coding for collagen VI subunits are responsible for this disease. A genome-wide scan established linkage of two CMDH families to a region on chromosome 3p23-21. Further linkage analysis confirmed that all families are linked to the same region (log of the odds score of 5.3). Haplotype analysis defines a 1.6-cM candidate interval and suggests that two common mutations may account for 78% of carrier chromosomes. This study describes and maps a new form of recessive CMD with joint hyperlaxity distinct from Ullrich and Bethlem myopathies with a founder effect in the French-Canadian population.

BACKGROUND:Hereditary sensory and autonomic neuropathy type 2 (HSAN2; MIM 201300) is a rare recessive neuropathy typically diagnosed in the first decade. The 1973 study of a French Canadian family led to the definition of HSAN2. OBJECTIVES:To demonstrate that the apparent higher prevalence of HSAN2 in Quebec is due to the presence of two HSN2 mutations and that carriers of different mutations appear to have a similar phenotype. METHODS:Through attending physicians, the authors recruited French Canadian patients with HSAN2. Exclusion of linkage to the known HSAN loci and linkage to the HSAN2 was performed using standard methods. Sequencing of the HSN2 gene was used to uncover the causal mutations. RESULTS:A large cluster of HSAN2 patients comprising 16 affected individuals belonging to 13 families was identified. The mode of inheritance is clearly autosomal recessive. All patients originated from southern Quebec, and 75% are from the Lanaudière region. Whereas linkage to the HSAN1, 3, and 4 loci was excluded, linkage to the 12p13.33 HSAN2 locus was confirmed. Sequencing of the HSN2 gene uncovered two French Canadian mutations and a novel nonsense mutation in a patient of Lebanese origin, all predicted to lead to truncations of the HSN2 protein. The comparison of clinical variables between patients with different genotypes does not suggest any difference in phenotype. CONCLUSIONS:Two founder mutations are responsible for the apparently higher prevalence of HSAN2 in French Canadians. Genotype-phenotype correlation does not suggest any significant clinical variability.

Hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum (OMIM 218000) is an autosomal recessive disease of early onset characterized by a delay in developmental milestones, a severe sensory-motor polyneuropathy with areflexia, a variable degree of agenesis of the corpus callosum, amyotrophy, hypotonia, and cognitive impairment. Although this disorder has rarely been reported worldwide, it has a high prevalence in the Saguenay-Lac-St-Jean region of the province of Quebec (Canada) predominantly because of a founder effect. The gene defect responsible for this disorder recently has been identified, and it is a protein-truncating mutation in the SLC12A6 gene, which codes for a cotransporter protein known as KCC3. Herein, we provide the first extensive review of this disorder, covering epidemiological, clinical, and molecular genetic studies.

We conducted a double-blind placebo study to investigate the claim that hyperbaric oxygen treatment (HBO2) improves the cognitive status of children with cerebral palsy (CP). Of 111 children diagnosed with CP (aged 4 to 12 years), only 75 were suitable for neuropsychological testing, assessing attention, working memory, processing speed, and psychosocial functioning. The children received 40 sessions of HBO2 or sham treatment over a 2-month period. Children in the active treatment group were exposed for 1 hour to 100% oxygen at 1.75 atmospheres absolute (ATA), whereas those in the sham group received only air at 1.3 ATA. Children in both groups showed better self-control and significant improvements in auditory attention and visual working memory compared with the baseline. However, no statistical difference was found between the two treatments. Furthermore, the sham group improved significantly on eight dimensions of the Conners' Parent Rating Scale, whereas the active treatment group improved only on one dimension. Most of these positive changes persisted for 3 months. No improvements were observed in either group for verbal span, visual attention, or processing speed.

Background The use of hyperbaric oxygen for children with cerebral palsy has spread worldwide, despite little scientific evidence of efficacy. We did a randomised trial to assess the efficacy and side-effects of this form of therapy in children with cerebral palsy.Methods 111 children with cerebral palsy aged 3-12 years were randomly assigned hyperbaric oxygen (n=57) or slightly pressurised room air (n=54). All children received 40 treatments over 2 months. Hyperbaric oxygen treatment was Ih in 100% oxygen at 1.75 atmospheres absolute (ATA); children on slightly pressurised air received air at 1.3 ATA (the lowest pressure at which pressure can be felt, thereby ensuring the maintenance of masking). The main outcome measure was gross motor function. Secondary outcomes included performance in activities of daily living, attention, working memory, and speech.Findings For all outcomes, both groups improved over the course of the study, but without any difference between the two treatments. The score on the global gross motor function measure increased by 3.0% in the children on slightly pressurised air and 2.9% in those on hyperbaric oxygen. The mean difference between treatments was -0.40 (95% CI -1.69 to 0.90, p=0.544). Other changes were seen in speech, attention, memory, and functional skills. Ear problems occurred in 27 children treated by hyperbaric oxygen and in 15 treated with hyperbaric air (p=0.004).Interpretation In this study, hyperbaric oxygen did not improve the condition of children with cerebral palsy compared with slightly pressurised air. The improvement seen in both groups for all dimensions tested deserves further consideration.