35 results on '"Nicolas Chrestian"'
Search Results
2. A founder mutation in the PLPBP gene in families from Saguenay‐Lac‐St‐Jean region affected by a pyridoxine‐dependent epilepsy
- Author
-
Maitou Pal, Baiba Lace, Yvan Labrie, Nathalie Laflamme, Nadie Rioux, Samarth Thonta Setty, Marc‐Andre Dugas, Louise Gosselin, Arnaud Droit, Nicolas Chrestian, and Serge Rivest
- Subjects
PLPBP ,PROSC ,vitamin B6‐dependent early‐onset epilepsy ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 ,Genetics ,QH426-470 - Abstract
Abstract Pyridoxine‐dependent epilepsy (PDE) is a relatively rare subgroup of epileptic disorders. They generally present in infancy as an early onset epileptic encephalopathy or seizures, refractory to standard treatments, with rapid and variable responses to vitamin B6 treatment. Whole exome sequencing of three unrelated families identified homozygous pathogenic mutation c.370_373del, p.Asp124fs in PLPBP gene in five persons. Haplotype analysis showed a single shared profile for the affected persons and their parents, leading to a hypothesis about founder effect of the mutation in Saguenay‐Lac‐St‐Jean region of French Canadians. All affected probands also shared one single mitochondrial haplotype T2b3 and two rare variations in the mitochondrial genome m.801A>G and m.5166A>G suggesting that a single individual female introduced PLPBP mutation c.370_373del, p.Asp124fs in Quebec. The mutation p.Asp124fs causes a severe disease phenotype with delayed myelination and cortical/subcortical brain atrophy. The most noteworthy radiological finding in this Quebec founder mutation is the presence of the temporal cysts that can be used as a marker of the disease. Also, both patients, who are alive, had a history of prenatal supplements taken by their mothers as antiemetic medication with high doses of pyridoxine. In the context of suspected PDE in patients with neonatal refractory seizures, treatment with pyridoxine and/or Pyridoxal‐5‐phophate has to be started immediately and continued until the results of genetic analysis received. Even with early appropriate treatment, neurological outcome of our patient is still poor.
- Published
- 2021
- Full Text
- View/download PDF
3. Case Report: Two Families With HPDL Related Neurodegeneration
- Author
-
Ieva Micule, Baiba Lace, Nathan T. Wright, Nicolas Chrestian, Jurgis Strautmanis, Mikus Diriks, Janis Stavusis, Dita Kidere, Elfa Kleina, Anna Zdanovica, Nataly Laflamme, Nadie Rioux, Samarth Thonta Setty, Sander Pajusalu, Arnaud Droit, Monkol Lek, Serge Rivest, and Inna Inashkina
- Subjects
spastic paraplegia ,ataxia ,citrate-synthase ,mitochondrial diseases ,brain diseases ,Genetics ,QH426-470 - Abstract
There are recent reports of associations of variants in the HPDL gene with a hereditary neurological disease that presents with a wide spectrum of clinical severity, ranging from severe neonatal encephalopathy with no psychomotor development to adolescent-onset uncomplicated spastic paraplegia. Here, we report two probands from unrelated families presenting with severe and intermediate variations of the clinical course. A homozygous variant in the HPDL gene was detected in each proband; however, there was no known parental consanguinity. We also highlight reductions in citrate synthase and mitochondrial complex I activity detected in both probands in different tissues, reflecting the previously proposed mitochondrial nature of disease pathogenesis associated with HPDL mutations. Further, we speculate on the functional consequences of the detected variants, although the function and substrate of the HPDL enzyme are currently unknown.
- Published
- 2022
- Full Text
- View/download PDF
4. Whole-exome sequencing identifies homozygous mutation in TTI2 in a child with primary microcephaly: a case report
- Author
-
Vincent Picher-Martel, Yvan Labrie, Serge Rivest, Baiba Lace, and Nicolas Chrestian
- Subjects
TTI2 ,Microcephaly ,Whole-exome sequencing ,Case report ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Primary microcephaly is defined as reduced occipital-frontal circumference noticeable before 36 weeks of gestation. Large amount of insults might lead to microcephaly including infections, hypoxia and genetic mutations. More than 16 genes are described in autosomal recessive primary microcephaly. However, the cause of microcephaly remains unclear in many cases after extensive investigations and genetic screening. Case presentation Here, we described the case of a boy with primary microcephaly who presented to a neurology clinic with short stature, global development delay, dyskinetic movement, strabismus and dysmorphic features. We performed microcephaly investigations and genetic panels. Then, we performed whole-exome sequencing to identify any genetic cause. Microcephaly investigations and genetic panels were negative, but we found a new D317V homozygous mutation in TELOE-2 interacting protein 2 (TTI2) gene by whole-exome sequencing. TTI2 is implicated in DNA damage response and mutation in that gene was previously described in mental retardation, autosomal recessive 39. Conclusions We described the first French Canadian case with primary microcephaly and global developmental delay secondary to a new D317V homozygous mutation in TTI2 gene. Our report also highlights the importance of TTI2 protein in brain development.
- Published
- 2020
- Full Text
- View/download PDF
5. A Homozygous Deep Intronic Mutation Alters the Splicing of Nebulin Gene in a Patient With Nemaline Myopathy
- Author
-
Nathalie Laflamme, Baiba Lace, Samarth Thonta Setty, Nadie Rioux, Yvan Labrie, Arnaud Droit, Nicolas Chrestian, and Serge Rivest
- Subjects
nemalin myopathy ,neuromuscular disorder ,alternative splicing ,nebulin isoforms ,nebulin ,NEB ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Nemaline myopathy is a rare disorder affecting the muscle sarcomere. Mutations in nebulin gene (NEB) are known to be responsible for about 50% of nemaline myopathy cases. Nebulin is a giant protein which is formed integrally with the sarcomeric thin filament. This complex gene is under extensive alternative splicing giving rise to multiple isoforms. In this study, we report a 6-year-old boy presenting with general muscular weaknesses. Identification of rod-shaped structures in the patient' biopsy raised doubt about the presence of a nemaline myopathy. Next-generation sequencing was used to identify a causative mutation for the patient syndrome. A homozygous deep intronic substitution was found in the intron 144 of the NEB. The variant was predicted by in silico tools to create a new donor splice site. Molecular analysis has shown that the mutation could alter splicing events of the nebulin gene leading to a significant decrease of isoforms level. This change in the expression level of nebulin could give rise to functional consequences in the sarcomere. These results are consistent with the phenotypes observed in the patient. Such a discovery of variants in this gene will allow a better understanding of the involvement of nebulin in neuromuscular diseases and help find new treatments for the nemaline myopathy.
- Published
- 2021
- Full Text
- View/download PDF
6. Adrenal insufficiency among children treated with hormonal therapy for infantile spasms
- Author
-
Gabrielle Doré‐Brabant, Geneviève Laflamme, Maude Millette, Bradley Osterman, and Nicolas Chrestian
- Subjects
Neurology ,Adrenocorticotropic Hormone ,Hydrocortisone ,Adrenal Cortex Hormones ,Prednisolone ,Humans ,Infant ,Prednisone ,Neurology (clinical) ,Child ,Spasms, Infantile ,Adrenal Insufficiency ,Retrospective Studies - Abstract
Hormonal therapy is a standard treatment for children with infantile spasms. However, the high doses given and long treatment duration expose patients to the risk of adrenal insufficiency (AI). This study aims to quantify the cumulative incidence of AI among children with infantile spasms treated with high-dose corticosteroids and/or adrenocorticotropic hormone.A retrospective chart review of patients treated for infantile spasms was performed between January 2009 and March 2020 in one pediatric specialized hospital. Variables collected include patient and treatment characteristics, risk factors of AI, and adrenal function testing. Analysis included descriptive statistics such as incidence and bivariate analysis.Thirty-one patients were included and received a total of 33 courses of treatment (17 corticosteroids [prednisone/prednisolone], 12 adrenocorticotropic hormone, and four combined). Physiologic hydrocortisone replacement therapy with stress supplementation was received after 32 of 33 (97%) courses of treatment. Adrenal function was assessed in 32 of 33 (97%) and AI occurred in 25 of 33 (76%, 95% confidence interval = 58-89). No predictive factor of AI was identified after hormonal treatment. No drug regimen was found to be safe. The two patients who developed an acute adrenal crisis presented to the emergency room within the days (between 2 and 7) following weaning off of hormonal treatment. They were the youngest children of the cohort, and both received prednisolone.Adrenal insufficiency is frequent and can potentially lead to an adrenal crisis in this population. This study highlights the necessity of hydrocortisone replacement therapy until AI has been excluded in a patient who has received hormonal therapy to treat infantile spasms. As such, routine laboratory assessment of adrenal function should be done in all patients.
- Published
- 2022
7. A founder mutation in the PLPBP gene in families from Saguenay‐Lac‐St‐Jean region affected by a pyridoxine‐dependent epilepsy
- Author
-
Marc Andre Dugas, Arnaud Droit, Yvan Labrie, Maitou Pal, Nicolas Chrestian, Nadie Rioux, Nathalie Laflamme, Samarth Thonta Setty, Serge Rivest, Louise Gosselin, and Baiba Lace
- Subjects
Proband ,Research Report ,PLPBP ,Pediatrics ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Context (language use) ,QH426-470 ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Diseases of the endocrine glands. Clinical endocrinology ,PROSC ,Epilepsy ,vitamin B6‐dependent early‐onset epilepsy ,Genetics ,Internal Medicine ,Medicine ,Pyridoxine-dependent epilepsy ,Exome sequencing ,business.industry ,Haplotype ,Research Reports ,RC648-665 ,medicine.disease ,Mutation (genetic algorithm) ,business ,Founder effect - Abstract
Pyridoxine‐dependent epilepsy (PDE) is a relatively rare subgroup of epileptic disorders. They generally present in infancy as an early onset epileptic encephalopathy or seizures, refractory to standard treatments, with rapid and variable responses to vitamin B6 treatment. Whole exome sequencing of three unrelated families identified homozygous pathogenic mutation c.370_373del, p.Asp124fs in PLPBP gene in five persons. Haplotype analysis showed a single shared profile for the affected persons and their parents, leading to a hypothesis about founder effect of the mutation in Saguenay‐Lac‐St‐Jean region of French Canadians. All affected probands also shared one single mitochondrial haplotype T2b3 and two rare variations in the mitochondrial genome m.801A>G and m.5166A>G suggesting that a single individual female introduced PLPBP mutation c.370_373del, p.Asp124fs in Quebec. The mutation p.Asp124fs causes a severe disease phenotype with delayed myelination and cortical/subcortical brain atrophy. The most noteworthy radiological finding in this Quebec founder mutation is the presence of the temporal cysts that can be used as a marker of the disease. Also, both patients, who are alive, had a history of prenatal supplements taken by their mothers as antiemetic medication with high doses of pyridoxine. In the context of suspected PDE in patients with neonatal refractory seizures, treatment with pyridoxine and/or Pyridoxal‐5‐phophate has to be started immediately and continued until the results of genetic analysis received. Even with early appropriate treatment, neurological outcome of our patient is still poor.
- Published
- 2021
8. Stress in Parents of Children With Genetically Determined Leukoencephalopathies: A Pilot Study
- Author
-
Aaron Spahr, E. Malvey-Dorn, S. Chandratre, F Pelletier, B. Osterman, M. Desmeules, G. Roedde, Marie Emmanuelle Dilenge, S. Chenier, Albert Larbrisseau, P. Marois, A Mirchi, Luan Tran, Elsa Rossignol, K. Y. Lim, Nancy Braverman, E. Dermer, Michael Shevell, J. Reggin, Mark A. Tarnopolsky, Guillaume Sébire, J. Laflamme, Kether Guerrero, Catalina Maftei, Geneviève Legault, Soad M. Ahmed, Sunita Venkateswaran, Daniela Pohl, Daniela Buhas, Philippe Major, I. Paradis, John J. Mitchell, Geneviève Bernard, M. Sullivan, Bernard Brais, Nicolas Chrestian, Myriam Srour, Michel Sylvain, EM Riou, and A. Nadeau
- Subjects
Adult ,Male ,Parents ,0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,Pilot Projects ,Early death ,030105 genetics & heredity ,White matter ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Leukoencephalopathies ,Surveys and Questionnaires ,Stress (linguistics) ,Humans ,Medicine ,Child ,business.industry ,Leukodystrophy ,Infant ,medicine.disease ,Cross-Sectional Studies ,medicine.anatomical_structure ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Female ,Neurology (clinical) ,Parental stress ,business ,Stress, Psychological ,030217 neurology & neurosurgery - Abstract
Genetically determined leukoencephalopathies comprise a group of rare inherited white matter disorders. The majority are progressive diseases resulting in early death. We performed a cross-sectional pilot study including 55 parents from 36 families to assess the level of stress experienced by parents of patients with genetically determined leukoencephalopathies, aged 1 month to 12 years. Thirty-four mothers and 21 fathers completed the Parenting Stress Index–4th Edition. One demographic questionnaire was completed per family. Detailed clinical data was gathered on all patients. Statistical analysis was performed with total stress percentile score as the primary outcome. Mothers and fathers had significantly higher stress levels compared with the normative sample; 20% of parents had high levels of stress whereas 11% had clinically significant levels of stress. Mothers and fathers had comparable total stress percentile scores. We identified pediatric behavioral difficulties and gross motor function to be factors influencing stress in mothers. Our study is the first to examine parental stress in this population and highlights the need for parental support early in the disease course. In this pilot study, we demonstrated that using the Parenting Stress Index–4th Edition to assess stress levels in parents of patients with genetically determined leukoencephalopathies is feasible, leads to valuable and actionable results, and should be used in larger, prospective studies.
- Published
- 2020
9. A National Spinal Muscular Atrophy Registry for Real-World Evidence
- Author
-
Laura McAdam, James J. Dowling, Monique Taillon, Anna McCormick, Said M’dahoma, Gerald Pfeffer, Cam-Tu Emilie Nguyen, Colleen O'Connell, Craig Campbell, Scott Worley, Hernan Gonorazky, Alex MacKenzie, Aaron Izenberg, Jiri Vajsar, Peter Dobrowolski, Emily Butler, Jean K. Mah, Simona Hasal, Alier Marerro, Hugh J. McMillan, Garth Smith, Erin K. O'Ferrall, Hanns Lochmüller, Michelle M. Mezei, Christen Shoesmith, Nicolas Dupré, Victoria Hodgkinson, Nicolas Chrestian, Louise R. Simard, Meghan Crone, Cecile Phan, Jodi Warman Chardon, Xavier Rodrigue, Jordan Sheriko, Michel Melanson, Kathy Selby, Angela Genge, Edward Leung, Maryam Oskoui, Kristine M. Chapman, Stephanie Plamondon, Kerri Schellenberg, Rami Massie, Bernard Brais, Joshua J. Lounsberry, Susan Dojeiji, Sean W. Taylor, Wendy Johnston, Chantal Poulin, and Lawrence Korngut
- Subjects
Registry ,Canada ,medicine.medical_specialty ,Neuromuscular disease ,Population ,Pediatrics ,Muscular Atrophy, Spinal ,Rare Diseases ,Humans ,Medicine ,Prospective Studies ,Registries ,Child ,Adverse effect ,education ,Real-world evidence ,education.field_of_study ,business.industry ,General Medicine ,Spinal muscular atrophy ,medicine.disease ,SMA ,Clinical trial ,Neurology ,Family medicine ,Original Article ,Observational study ,Neurology (clinical) ,business ,Rare disease - Abstract
Background:Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.Methods:The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.Results:The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.Conclusion:Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
- Published
- 2020
10. Whole-exome sequencing identifies homozygous mutation in TTI2 in a child with primary microcephaly: a case report
- Author
-
Serge Rivest, Yvan Labrie, Nicolas Chrestian, Vincent Picher-Martel, and Baiba Lace
- Subjects
Male ,Microcephaly ,Canada ,Brain development ,Primary microcephaly ,Nervous System Malformations ,Short stature ,lcsh:RC346-429 ,03 medical and health sciences ,0302 clinical medicine ,Exome Sequencing ,Case report ,Medicine ,Humans ,Global developmental delay ,Genetic Testing ,Gene ,Exome sequencing ,lcsh:Neurology. Diseases of the nervous system ,030304 developmental biology ,Genetics ,0303 health sciences ,business.industry ,Homozygote ,Infant ,General Medicine ,TTI2 ,medicine.disease ,3. Good health ,Child, Preschool ,Whole-exome sequencing ,Mutation ,French canadian ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Background Primary microcephaly is defined as reduced occipital-frontal circumference noticeable before 36 weeks of gestation. Large amount of insults might lead to microcephaly including infections, hypoxia and genetic mutations. More than 16 genes are described in autosomal recessive primary microcephaly. However, the cause of microcephaly remains unclear in many cases after extensive investigations and genetic screening. Case presentation Here, we described the case of a boy with primary microcephaly who presented to a neurology clinic with short stature, global development delay, dyskinetic movement, strabismus and dysmorphic features. We performed microcephaly investigations and genetic panels. Then, we performed whole-exome sequencing to identify any genetic cause. Microcephaly investigations and genetic panels were negative, but we found a new D317V homozygous mutation in TELOE-2 interacting protein 2 (TTI2) gene by whole-exome sequencing. TTI2 is implicated in DNA damage response and mutation in that gene was previously described in mental retardation, autosomal recessive 39. Conclusions We described the first French Canadian case with primary microcephaly and global developmental delay secondary to a new D317V homozygous mutation in TTI2 gene. Our report also highlights the importance of TTI2 protein in brain development.
- Published
- 2020
11. ABHD16A deficiency causes a complicated form of hereditary spastic paraplegia associated with intellectual disability and cerebral anomalies
- Author
-
Aren E Marshall, Nadie Rioux, Adrie D Dane, Tipu Sultan, Kristin D. Kernohan, Nataly Laflamme, Lauren Brady, Cynthia J. Curry, Taila Hartley, Kym M. Boycott, Nicolas Chrestian, Alexa Derksen, Frédéric M. Vaz, Maha S. Zaki, Geneviève Bernard, Joseph G. Gleeson, Gabrielle Lemire, Yoko Ito, H. T. Hutchison, Wendy Mears, Lynn Pais, Mark A. Tarnopolsky, Valentina Stanley, Laboratory Genetic Metabolic Diseases, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, APH - Personalized Medicine, and APH - Methodology
- Subjects
Adult ,Male ,Adolescent ,lysophosphatidylserine ,Hereditary spastic paraplegia ,Central nervous system ,Corpus callosum ,Bioinformatics ,White matter ,Cohort Studies ,Young Adult ,Leukoencephalopathies ,Report ,Intellectual disability ,Genetics ,Medicine ,Humans ,Global developmental delay ,hereditary spastic paraplegia ,Child ,Genetics (clinical) ,business.industry ,Spastic Paraplegia, Hereditary ,Cerebral Palsy ,ABHD16A ,medicine.disease ,Monoacylglycerol Lipases ,Pedigree ,medicine.anatomical_structure ,Phenotype ,intellectual disability ,Child, Preschool ,Mutation ,Etiology ,Progressive spasticity ,Female ,business - Abstract
ABHD16A (abhydrolase domain-containing protein 16A, phospholipase) encodes the major phosphatidylserine (PS) lipase in the brain. PS lipase synthesizes lysophosphatidylserine, an important signaling lipid that functions in the mammalian central nervous system. ABHD16A has not yet been associated with a human disease. In this report, we present a cohort of 11 affected individuals from six unrelated families with a complicated form of hereditary spastic paraplegia (HSP) who carry bi-allelic deleterious variants in ABHD16A. Affected individuals present with a similar phenotype consisting of global developmental delay/intellectual disability, progressive spasticity affecting the upper and lower limbs, and corpus callosum and white matter anomalies. Immunoblot analysis on extracts from fibroblasts from four affected individuals demonstrated little to no ABHD16A protein levels compared to controls. Our findings add ABHD16A to the growing list of lipid genes in which dysregulation can cause complicated forms of HSP and begin to describe the molecular etiology of this condition.
- Published
- 2021
12. The Canadian Neuromuscular Disease Registry 2010-2019: A Decade of Facilitating Clinical Research Througha Nationwide, Pan-NeuromuscularDisease Registry
- Author
-
Tim Benstead, Hernan Gonorazky, C. Krieger, Victoria Hodgkinson, Said M’dahoma, E. Leung, Aaron Izenberg, Angela Russell, Gerald Pfeffer, Kristine M. Chapman, A. Marrero, James J. Dowling, H. Briemberg, Monique Taillon, Lorne Zinman, Nicolas Chrestian, Angela Genge, Nicolas Dupré, Simona Hasal, Agessandro Abrahao, G. Matte, S. Dojeiji, Shannon L. Venance, C. Campbell, S. Botez, Hans D. Katzberg, R.G. Smith, Maryam Oskoui, Erin K. O'Ferrall, Alex MacKenzie, I. Grant, G. Linassi, Colleen O'Connell, P.R. Bourque, J. K. Mah, Xavier Rodrigue, Scott Worley, Michel Melanson, S. Taylor, Anna McCormick, Kerri Schellenberg, Laura McAdam, Christen Shoesmith, Stephanie Plamondon, Joshua J. Lounsberry, C. Phan, Kathy Selby, Rami Massie, M. Crone, H. McMillan, Bernard Brais, G. Jewett, Peter Dobrowolski, Jordan Sheriko, Wendy Johnston, Jodi Warman-Chardon, Lawrence Korngut, Neil R. Cashman, S. Kalra, Hanns Lochmüller, Michelle M. Mezei, C. T. Nguyen, and Chantal Poulin
- Subjects
0301 basic medicine ,Research Report ,Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Canada ,Registry ,Neuromuscular disease ,Adolescent ,Duchenne muscular dystrophy ,Myotonic dystrophy ,Muscular Atrophy, Spinal ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,medicine ,Humans ,Myotonic Dystrophy ,Registries ,Amyotrophic lateral sclerosis ,Child ,real-world evidence ,Aged ,Aged, 80 and over ,business.industry ,Amyotrophic Lateral Sclerosis ,Infant ,Spinal muscular atrophy ,Middle Aged ,medicine.disease ,Natural history ,Muscular Dystrophy, Duchenne ,030104 developmental biology ,Clinical research ,Neurology ,Muscular Dystrophies, Limb-Girdle ,natural history ,Child, Preschool ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Limb-girdle muscular dystrophy - Abstract
We report the recruitment activities and outcomes of a multi-disease neuromuscular patient registry in Canada. The Canadian Neuromuscular Disease Registry (CNDR) registers individuals across Canada with a confirmed diagnosis of a neuromuscular disease. Diagnosis and contact information are collected across all diseases and detailed prospective data is collected for 5 specific diseases: Amyotrophic Lateral Sclerosis (ALS), Duchenne Muscular Dystrophy (DMD), Myotonic Dystrophy (DM), Limb Girdle Muscular Dystrophy (LGMD), and Spinal Muscular Atrophy (SMA). Since 2010, the CNDR has registered 4306 patients (1154 pediatric and 3148 adult) with 91 different neuromuscular diagnoses and has facilitated 125 projects (73 academic, 3 not-for-profit, 3 government, and 46 commercial) using registry data. In conclusion, the CNDR is an effective and productive pan-neuromuscular registry that has successfully facilitated a substantial number of studies over the past 10 years.
- Published
- 2021
13. The Occurrence of FUS Mutations in Pediatric Amyotrophic Lateral Sclerosis: A Case Report and Review of the Literature
- Author
-
Francis Brunet, Vincent Picher-Martel, Nicolas Chrestian, and Nicolas Dupré
- Subjects
0301 basic medicine ,Male ,Pediatrics ,medicine.medical_specialty ,Adolescent ,SOD1 ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Family history ,Amyotrophic lateral sclerosis ,Mutation ,business.industry ,Superoxide Dismutase ,Amyotrophic Lateral Sclerosis ,DNA Helicases ,medicine.disease ,Phenotype ,Multifunctional Enzymes ,030104 developmental biology ,Pediatrics, Perinatology and Child Health ,RNA-Binding Protein FUS ,Neurology (clinical) ,Sarcoma ,Differential diagnosis ,business ,030217 neurology & neurosurgery ,RNA Helicases ,Pediatric population - Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease affecting both upper and lower motor neurons and leading to progressive paralysis. Most cases are sporadic, and the symptoms generally begin in the sixth or seventh decade. Juvenile ALS appears in a rare subgroup of patients with onset before the age of 25 years old. Contrary to the classical adult phenotype where 90% of cases are sporadic, most cases of juvenile ALS are caused by a genetic mutation in either SOD1 (superoxide dismutase one), SETX (senataxin), or FUS (fused in sarcoma). In the pediatric population, ALS is more infrequent and rarely considered in the differential diagnosis. There are few reports of ALS in children. Here, we describe a 14-year-old boy with a very fast progressing classical ALS phenotype and tremor caused by a c.1554_1557delACAG mutation in FUS. Our review of the literature advocates that pediatric ALS is highly suggestive of FUS mutations and that gene should be tested in children presenting with symptoms of ALS. The children with FUS-related ALS may have no family history and present initially with learning disabilities, tremor, and mild motor developmental delay.
- Published
- 2020
14. Characterization of the phenotype with cognitive impairment and protein mislocalization in SCA34
- Author
-
Christian Martel, Guy A. Rouleau, Nicolas Dupré, Leila Sellami, Lydia Touzel-Deschênes, Kevin Lacroix, Robert Laforce, François Gros-Louis, Laurence Martineau, Andréane Lavallée, Gabrielle Houle, Marie Beaudin, and Nicolas Chrestian
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Article ,03 medical and health sciences ,Dysarthria ,0302 clinical medicine ,Erythrokeratodermia variabilis ,medicine ,Genetics (clinical) ,Cellular localization ,Cerebellar ataxia ,business.industry ,Limb ataxia ,medicine.disease ,030104 developmental biology ,Spinocerebellar ataxia ,Cerebellar atrophy ,Neurology (clinical) ,medicine.symptom ,business ,Neurocognitive ,030217 neurology & neurosurgery - Abstract
ObjectiveTo better characterize the neurologic and cognitive profile of patients with spinocerebellar ataxia 34 (SCA34) caused by ELOVL4 mutations and to demonstrate the presence of ELOVL4 cellular localization and distribution abnormalities in skin-derived fibroblasts.MethodsWe investigated a 5-generation French-Canadian kindred presenting with a late-onset cerebellar ataxia and recruited age- and education-matched controls to evaluate the presence of neurocognitive impairment. Immunohistochemistry of dermal fibroblasts derived from a patient's skin biopsy was performed.ResultsPatients had a late-onset slowly progressive cerebellar syndrome (mean age at onset 47 years; range 32–60 years) characterized by truncal and limb ataxia, dysarthria, hypometric saccades, and saccadic pursuits. No patient had past or current signs of erythrokeratodermia variabilis, which had previously been reported. MRI revealed cerebellar atrophy, with pontine atrophy (4 of 6 patients), and cruciform hypersignal in the pons (2 of 6 patients). Fluorodeoxyglucose-PET showed diffuse cerebellar hypometabolism in all 5 tested patients with subtle parietal hypometabolism in 3. Significant cognitive deficits were found in executive functioning, along with apparent visuospatial, attention, and psychiatric involvement. Immunohistochemistry of dermal fibroblasts showed mislocalization of the ELOVL4 protein, which appeared punctate and aggregated, supporting a dominant negative effect of the mutation on protein localization.ConclusionsOur findings support the pathogenicity of ELOVL4 mutations in cerebellar dysfunction and provide a detailed characterization of the SCA34 phenotype, with neurocognitive changes typical of the cerebellar cognitive-affective syndrome.
- Published
- 2020
15. Collagen VI-related limb-girdle syndrome caused by frequent mutation in COL6A3 gene with conflicting reports of pathogenicity
- Author
-
Cristina Domínguez-González, Janis Stavusis, Volker Straub, Luísa Panadés-de Oliveira, Ana Töpf, Nicolas Chrestian, Nathan T. Wright, Dita Kidere, Ieva Micule, Baiba Lace, and Inna Inashkina
- Subjects
0301 basic medicine ,Adult ,Male ,Bethlem Myopathy 1 ,Contracture ,Ullrich congenital muscular dystrophy ,Collagen Type VI ,Biology ,Compound heterozygosity ,Muscular Dystrophies ,03 medical and health sciences ,0302 clinical medicine ,Von Willebrand factor ,Collagen VI ,Exome Sequencing ,medicine ,Humans ,Myopathy ,Genetics (clinical) ,Genetics ,Sclerosis ,Middle Aged ,medicine.disease ,Limb-Girdle Syndrome ,Pedigree ,030104 developmental biology ,Neurology ,Pediatrics, Perinatology and Child Health ,Mutation (genetic algorithm) ,biology.protein ,Female ,Neurology (clinical) ,medicine.symptom ,030217 neurology & neurosurgery - Abstract
Recently the scientific community has started to view Bethlem myopathy 1 and Ullrich congenital muscular dystrophy as two extremes of a collagen VI-related myopathy spectrum rather than two separate entities, as both are caused by mutations in one of the collagen VI genes. Here we report three individuals in two families who are homozygous for a COL6A3 mutation (c.7447A> G; p.Lys2483Glu), and compare their clinical features with seven previously published cases. Individuals carrying homozygous or compound heterozygous c.7447A> G, (p.Lys2483Glu) mutation exhibit mild phenotype without loss of ambulation, similar to the cases described previously as Collagen VI-related limb-girdle syndrome. The phenotype could arise due to an aberrant assembly of Von Willebrand factor A domains. Based on these data, we propose that c.7447A> G, (p.Lys2483Glu) is a common pathogenic mutation.
- Published
- 2019
16. 71 Adrenal Insufficiency among Children treated with Hormonal Therapy for Infantile Spasms
- Author
-
Nicolas Chrestian, Geneviève Laflamme, Maude Millette, Bradley Osterman, and Gabrielle Doré-Brabant
- Subjects
Pediatrics ,medicine.medical_specialty ,business.industry ,Pediatrics, Perinatology and Child Health ,Adrenal insufficiency ,medicine ,Hormonal therapy ,medicine.disease ,business - Abstract
Primary Subject area Endocrinology and Metabolism Background Hormonal therapy is a standard treatment for children with infantile spasms. However, the high doses given and long treatment duration exposes patients to the potential risk of adrenal insufficiency (AI). There is, presently, limited data on occurrence of AI after hormonal therapy in this population. Objectives This study aims to quantify the incidence of AI among children with infantile spasms treated with high-dose corticosteroids and/or adrenocorticotropic hormone (ACTH). Design/Methods A retrospective chart review of patients less than 2 years old treated for infantile spasms was performed between January 2009 to March 2020 in one pediatric specialized hospital. Variables collected included sex, age, etiology, age at treatment initiation, type of hormonal treatment, dose and duration of treatment, concomitant medication and illness, other corticosteroid uses, hydrocortisone replacement therapy use, adrenal function testing, and signs of AI. Analysis included descriptive statistics, such as incidence and bivariate analysis. Results Thirty-one patients met the inclusion criteria and received a total of 33 separated courses of hormonal treatment. Adrenal function following each course of treatment was evaluated in all patients, either by tests or by the presence of adrenal crisis. Oral hydrocortisone replacement therapy was received by 32/33 (97%) children. AI occurred in 25/33 (76% [95% CI 58-89]) children. There was no predictive factor for adrenal insufficiency after hormonal treatment, and no drug regimen (duration or total received dose) was safe. Two patients (6%) presented to the emergency room with an acute adrenal crisis the day following the weaning off of hormonal treatment. They were the youngest children of the cohort, with an age of 1,6 and 2,7 months at the initiation of treatment. All other patients were aged 4 months and older. Conclusion This study suggests that adrenal suppression is frequent after standard hormonal therapy regimen for infantile spasms. This can lead to serious complications, such as adrenal crisis, if not supplemented. A routine laboratory assessment of adrenal function should be done after hormonal therapy for all patients. We suggest that hydrocortisone replacement therapy should be given at the end of hormonal therapy and until testing results for adrenal function are obtained, particularly for younger patients.
- Published
- 2021
17. Novel Recessive TNNT1 Congenital Core-Rod Myopathy in French Canadians
- Author
-
Rebecca Robertson, Jason Karamchandani, Xavier Allard-Chamard, Marc Petitclerc, Benjamin Ellezam, Vandana Gupta, Denis Brunet, Nicolas Chrestian, Emily C Troiano, Bernard Brais, Marie-Josée Dicaire, Chamindra G. Konersman, Alan H. Beggs, David Pellerin, Jodi Warman Chardon, Asli Aykanat, and Jean Mathieu
- Subjects
0301 basic medicine ,Male ,Pathology ,medicine.medical_specialty ,Myopathies, Nemaline ,Rhabdomyolysis ,Article ,Morpholinos ,03 medical and health sciences ,0302 clinical medicine ,Nemaline myopathy ,Troponin T ,medicine ,Missense mutation ,Animals ,Humans ,RNA, Messenger ,Myopathy ,Child ,Muscle, Skeletal ,Zebrafish ,Muscle contracture ,Muscle biopsy ,medicine.diagnostic_test ,business.industry ,Skeletal muscle ,Middle Aged ,medicine.disease ,Congenital myopathy ,Magnetic Resonance Imaging ,030104 developmental biology ,medicine.anatomical_structure ,Neurology ,Gene Knockdown Techniques ,Female ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Objective Recessive null variants of the slow skeletal muscle troponin T1 (TNNT1) gene are a rare cause of nemaline myopathy that is fatal in infancy due to respiratory insufficiency. Muscle biopsy shows rods and fiber type disproportion. We report on 4 French Canadians with a novel form of recessive congenital TNNT1 core-rod myopathy. Methods Patients underwent full clinical characterization, lower limb magnetic resonance imaging (MRI), muscle biopsy, and genetic testing. A zebrafish loss-of-function model using morpholinos was created to assess the pathogenicity of the identified variant. Wild-type or mutated human TNNT1 mRNAs were coinjected with morpholinos to assess their abilities to rescue the morphant phenotype. Results Three adults and 1 child shared a novel missense homozygous variant in the TNNT1 gene (NM_003283.6: c.287T > C; p.Leu96Pro). They developed from childhood very slowly progressive limb-girdle weakness with rigid spine and disabling contractures. They suffered from restrictive lung disease requiring noninvasive mechanical ventilation in 3 patients, as well as recurrent episodes of rhabdomyolysis triggered by infections, which were relieved by dantrolene in 1 patient. Older patients remained ambulatory into their 60s. MRI of the leg muscles showed fibrofatty infiltration predominating in the posterior thigh and the deep posterior leg compartments. Muscle biopsies showed multiminicores and lobulated fibers, rods in half the patients, and no fiber type disproportion. Wild-type TNNT1 mRNA rescued the zebrafish morphants, but mutant transcripts failed to do so. Interpretation This study expands the phenotypic spectrum of TNNT1 myopathy and provides functional evidence for the pathogenicity of the newly identified missense mutation. ANN NEUROL 2020;87:568-583.
- Published
- 2019
18. CONGENITAL MYOPATHIES 1 – NEMALINE
- Author
-
Nicolas Chrestian, Y. Labrie, M. Dugas, S. Rivest, Baiba Lace, N. Laflamme, and N. Rioux
- Subjects
Neurology ,Pediatrics, Perinatology and Child Health ,Neurology (clinical) ,Genetics (clinical) - Published
- 2020
19. Hereditary neuropathy with liability to pressure palsies in childhood: Case series and literature update
- Author
-
Nicolas Chrestian, Craig Campbell, Hugh J. McMillan, Chantal Poulin, and Jiri Vajsar
- Subjects
Male ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Genetic counseling ,Neural Conduction ,Mononeuropathy ,medicine ,Humans ,Carpal tunnel ,Child ,Genetics (clinical) ,Arthrogryposis ,Palsy ,business.industry ,medicine.disease ,Median nerve ,Surgery ,medicine.anatomical_structure ,Neurology ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Female ,Neurology (clinical) ,Presentation (obstetrics) ,Hereditary Sensory and Motor Neuropathy ,business ,Polyneuropathy ,Brachial plexus ,Gene Deletion ,Myelin Proteins - Abstract
Hereditary Neuropathy with Liability to Pressure Palsy (HNPP) is a rare condition in childhood with a diverse range of clinical presentations. We analyzed the clinical presentation and electrophysiological data of 12 children with a confirmed PMP22 gene deletion and reviewed the published reports of HNPP in children and compared our data with the reports from the literature review. Peroneal palsy was the most common presentation (42%) followed by brachial plexus palsy in 25% of our cases. Nerve conduction studies were always suggestive of the diagnosis demonstrating 3 major patterns: multifocal demyelination at the area of entrapment, generalized sensory-motor polyneuropathy and a combination of the two first patterns in a vast majority (60%). Surprisingly, there was bilateral or unilateral electrophysiological entrapment of the median nerve at the carpal tunnel in all our patients. The clinical presentation of HNPP in childhood is heterogeneous and electrophysiological findings are helpful in establishing the diagnosis. Any unexplained mononeuropathy or multifocal neuropathy should lead to PMP22 gene testing to look for the deletion. Early diagnosis is important in order to facilitate appropriate genetic counseling and also for the appropriate care for these patients.
- Published
- 2015
20. Congenital Myopathies
- Author
-
Hernan Gonorazky, Jonathan B. Strober, James J. Dowling, Jahannaz Dastgir, and Nicolas Chrestian
- Subjects
business.industry ,Medicine ,business - Published
- 2017
21. Muscle hyperthrophy with RYR1 mutation
- Author
-
B. Lace, Nicolas Chrestian, P. Gould, and A. Dionne
- Subjects
Genetics ,RYR1 ,Neurology ,Pediatrics, Perinatology and Child Health ,Mutation (genetic algorithm) ,Neurology (clinical) ,Biology ,Genetics (clinical) - Published
- 2017
22. A new TNNT1 mutation in a non Amish patient with original muscle pathology findings
- Author
-
J. Karamchandani, M. Sylvain, and Nicolas Chrestian
- Subjects
Pathology ,medicine.medical_specialty ,Muscle pathology ,Neurology ,business.industry ,Pediatrics, Perinatology and Child Health ,Mutation (genetic algorithm) ,Medicine ,Neurology (clinical) ,business ,Bioinformatics ,Genetics (clinical) - Published
- 2017
23. Participation restriction in childhood phenotype of myotonic dystrophy type 1: a systematic retrospective chart review
- Author
-
Marie-Frédéric Bouchard, Marie Kierkegaard, Nicolas Chrestian, Cynthia Gagnon, Catherine Blackburn, Mélissa Lavoie, and Jean Mathieu
- Subjects
Adult ,Male ,Parents ,030506 rehabilitation ,medicine.medical_specialty ,Social stigma ,Adolescent ,media_common.quotation_subject ,Myotonic dystrophy ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Developmental Neuroscience ,Legal guardian ,medicine ,Humans ,Myotonic Dystrophy ,Young adult ,Psychiatry ,media_common ,Retrospective Studies ,business.industry ,Retrospective cohort study ,Middle Aged ,Social engagement ,medicine.disease ,Social Participation ,Friendship ,Phenotype ,Spouse ,Pediatrics, Perinatology and Child Health ,Female ,Neurology (clinical) ,0305 other medical science ,business ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
Aim Myotonic dystrophy type 1 (DM1), a neuromuscular disorder, is divided into four clinical phenotypes: congenital; childhood; adult-onset, and late-onset. Publications about the childhood phenotype, especially the long-term outcome, are scarce. The aims of this study were to assess and describe participation outcomes in adults with the childhood phenotype. Method A retrospective chart methodology. Data were extracted from health records for 63 adults with childhood DM1 (32 males, 31 females; mean age 34y, standard deviation [SD] 11y 6mo; range 18–54y) who had attended the Saguenay Neuromuscular Clinic, Canada. Results Thirty-four adults (54%) lived with their parents or in foster homes, and most patients needed services or help to live independently. A significant proportion (22%) were isolated in regard to friendship. Very few adults had children, although 33% lived with a spouse. The majority of patients (86%) relied on social security and only one person was currently working. Financial responsibilities were often an issue and 13 (21%) were under legal guardianship. Interpretation This study showed that patients with the childhood phenotype present a guarded prognosis regarding long-term social participation. These participation restrictions could be related to behavioural, cognitive, and social stigma problems in childhood. This study illustrates the absolute necessity to pursue an interdisciplinary follow-up of these patients when they are reaching adulthood.
- Published
- 2016
24. Clinical, electrophysiologic, and genetic study of non-dystrophic myotonia in French-Canadians
- Author
-
Jack Puymirat, Elsa Rossignol, Nicolas Dupré, Jean-Pierre Bouchard, Denis Brunet, Jean Mathieu, Bernard Brais, Damien Sternberg, and Nicolas Chrestian
- Subjects
Male ,DNA Mutational Analysis ,Physiology ,Audiology ,Sodium Channels ,Myotonia ,Genotype ,Repetitive nerve stimulation ,NAV1.4 Voltage-Gated Sodium Channel ,Genetics (clinical) ,Aged, 80 and over ,education.field_of_study ,Exercise Tolerance ,Muscle Weakness ,biology ,Quebec ,Middle Aged ,Cold Temperature ,Neurology ,Female ,Adult ,Genetic Markers ,musculoskeletal diseases ,medicine.medical_specialty ,Lid lag ,Population ,Young Adult ,Tongue ,Chloride Channels ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,Muscle, Skeletal ,education ,Aged ,Leg ,CLCN1 ,Myotonia congenita ,business.industry ,medicine.disease ,body regions ,Mutation ,Pediatrics, Perinatology and Child Health ,biology.protein ,Neurology (clinical) ,Percussion myotonia ,business - Abstract
Thirty-three French-Canadian families with non-dystrophic myotonia were identified. Fifty subjects were recruited and submitted to a complete clinical, electrophysiologic and genetic evaluation. Thirteen mutations were identified in CLCN1 and five mutations were identified in SCN4A. Onset in the lower extremities, presence of tongue myotonia and transient weakness suggested recessive CLCN1 mutations. Lid myotonia, absence of hypertrophy and exacerbation with cold temperature suggested SCN4A mutations. Pain was not a feature of dominant CLCN1 mutations while it could be seen in the others, more frequently in SCN4A mutations. Warm up phenomenon, hand grip myotonia, percussion myotonia, lid lag and hormonal effects were not distinguishing features. Repetitive nerve stimulation and short exercise test showed either a large (>50%) or mild-moderate (10–50%) decrement with recessive CLCN1 mutations while they showed only mild or no decrement with dominant CLCN1 and SCN4A mutations. The French-Canadian population shows wide phenotypic and genotypic heterogeneity in non-dystrophic myotonias.
- Published
- 2009
25. Ataxies, paraparésies spastiques et neuropathies héréditaires fréquentes dans l’Est du Canada
- Author
-
Jean-Pierre Bouchard, Bernard Brais, Nicolas Dupré, Guy A. Rouleau, Nicolas Chrestian, and Isabelle Thiffault
- Subjects
Genetics ,education.field_of_study ,Ataxia ,Population ,Spastic paraparesis ,Spinocerebellar Degenerations ,Hereditary Ataxias ,Neurology ,medicine ,In patient ,Neurology (clinical) ,medicine.symptom ,education ,Founder effect - Abstract
It has been demonstrated, for many inherited diseases, that historical events have shaped the various regional gene pools of Eastern Canada. In so doing, it has given rise to the increased prevalence of some rare diseases due, to founder effects. The following neurogenetic disorders were first identified in patients from Eastern Canada: AOA-2, Arsacs, HSN-2, Arca-1, HMSN/ACC and Arsal. The population of Eastern Canada, we are convinced, will still allow the identification of new rare forms of hereditary ataxias, spastic parapareses and neuropathies as well as contribute to the uncovering of their mutated genes. We have summarized our current knowledge of the various hereditary ataxias, spastic parapareses and neuropathies in Eastern Canada. The study of the more common and homogenous features of these diseases has been largely completed.
- Published
- 2008
26. A novel founder SCN4A mutation causes painful cold-induced myotonia in French-Canadians
- Author
-
Martine Tétreault, Nicolas Dupré, Jean Mathieu, Nicolas Chrestian, Marie-Josée Dicaire, Isabelle Thiffault, Bernard Brais, Jack Puymirat, and Elsa Rossignol
- Subjects
Adult ,Male ,musculoskeletal diseases ,congenital, hereditary, and neonatal diseases and abnormalities ,Adolescent ,Pain ,Myotonic dystrophy ,Sodium Channels ,White People ,Myotonia ,medicine ,Paralysis ,Humans ,NAV1.4 Voltage-Gated Sodium Channel ,Child ,Aged ,Aged, 80 and over ,Genetics ,CLCN1 ,biology ,Genetic heterogeneity ,business.industry ,Quebec ,Periodic paralysis ,Middle Aged ,medicine.disease ,Founder Effect ,Cold Temperature ,Paramyotonia congenita ,Child, Preschool ,Mutation ,biology.protein ,Female ,France ,Neurology (clinical) ,medicine.symptom ,business ,Founder effect - Abstract
Background: Myotonia is observed in classic congenital myotonia caused by CLCN1 mutations and in sodium-channel myotonia (SCM) due to SCN4A mutations. Methods: We assessed 66 electrically proven cases of myotonia belonging to 17 French-Canadian families living in the Saguenay Lac St-Jean area of Quebec, a region well known for its genetic founder effects. The CLCN1 gene was sequenced in one affected member of each family. SCN4A exons with known SCM mutations were subsequently sequenced in families where no CLCN1 mutations were found. Results: Six families, 33% of cases (22/66), presenting classic congenital myotonia phenotypes were found to carry two previously identified CLCN1 mutations. In the other 11 families comprising 66% of cases (44/66), a new dominant SCN4A mutation in exon 24 (M1476I) was uncovered and segregated with a variable SCM phenotype. Although all carriers of this novel mutation had electrical myotonia, some were asymptomatic (25%) and age at onset was variable in the others (5 to 67, mean 21). Cold aggravated myotonia was observed in 41% of cases and painful myotonia in 18%. Additional features observed include aggravation of symptoms with pregnancies (7%), localized muscle swelling (2%), myotonic reactions to anesthesia (2%), and food-induced paralysis (2%). Conclusions: This cohort is the largest described with a variable sodium-channel myotonia phenotype caused by a single SCN4A mutation. The clinical variability observed in this cohort underlines the phenotypic heterogeneity of SCN4A mutations and suggests that variants in other genes likely modulate clinical expression. GLOSSARY: DM1 = myotonic dystrophy type I; HYPP = hyperkaliemic periodic paralysis; PMC = paramyotonia congenita; SCM = sodium-channel myotonia; SLSJ = Saguenay Lac Saint-Jean.
- Published
- 2007
27. Clinical and genetic study of hereditary spastic paraplegia in Canada
- Author
-
Karim Mourabit-Amari, Pierre Provencher, Peter N. Ray, Jean-Denis Brisson, Anna Szuto, Patrick A. Dion, Noreen Mohsin, Nicolas Dupré, Shiyi Chen, Guy A. Rouleau, Anil Venkitachalam, Grace Yoon, Kym M. Boycott, Sohnee Ahmed, Dimitri J. Stavropoulos, Setareh Ashtiani, Oksana Suchowersky, Ziv Gan-Or, Heather MacDonald, Nicolas Chrestian, and Jodi Warman-Chardon
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Multivariate analysis ,Hereditary spastic paraplegia ,business.industry ,Odds ratio ,medicine.disease ,Article ,Confidence interval ,3. Good health ,03 medical and health sciences ,KIAA0196 ,030104 developmental biology ,0302 clinical medicine ,Internal medicine ,Cohort ,medicine ,Spastic ,Neurology (clinical) ,Paraplegia ,business ,030217 neurology & neurosurgery ,Genetics (clinical) - Abstract
Objective:To describe the clinical, genetic, and epidemiologic features of hereditary spastic paraplegia (HSP) in Canada and to determine which clinical, radiologic, and genetic factors determine functional outcomes for patients with HSP.Methods:We conducted a multicenter observational study of patients who met clinical criteria for the diagnosis of HSP in the provinces of Alberta, Ontario, and Quebec from 2012 to 2015. Characteristics of the participants were analyzed using descriptive statistics. The main outcome measure for a subset of the cohort (n = 48) was the Spastic Paraplegia Rating Scale. We also used the SPATAX-EUROSPA disability stage (disability score) to assess disability (n = 65).Results:A total of 526 patients were identified with HSP across the country, and 150 patients had a confirmed genetic diagnosis. Mutations were identified in 15 different genes; the most common were SPAST (SPG4, 48%), ATL1 (SPG3A, 16%), SPG11 (8%), SPG7 (7%), and KIAA0196 (SPG8, 5%). The diagnosis of SPG4 was associated with older age at symptom onset (p = 0.0017). SPG4 and SPG3A were less associated with learning disabilities compared to other subtypes of HSP, and SPG11 was strongly associated with progressive cognitive deficits (odds ratio 87.75, 95% confidence interval 14.04–548.24, p < 0.0001). SPG3A was associated with better functional outcomes compared to other HSP subtypes (p = 0.04) on multivariate analysis. The strongest predictor of significant disability was abnormal brain MRI (p = 0.014).Conclusions:The most important predictors of disability in our HSP cohort were SPG11 mutations and abnormal brain MRI. Accurate molecular characterization of well-phenotyped cohorts and international collaboration are essential to establish the natural history of these rare neurodegenerative disorders.
- Published
- 2016
28. Oculopharyngeal Muscular Dystrophy
- Author
-
Bernard Brais, Nicolas Chrestian, Nicolas Dupré, Jean-Pierre Bouchard, and Guy Rouleau
- Published
- 2013
29. A novel mutation in a large French-Canadian family with LGMD1B
- Author
-
Jean Champagne, Nicolas Dupré, Peter Gould, Paul N. Valdmanis, Denis Brunet, Jean-Pierre Bouchard, Najmeddine Echahidi, Nicolas Chrestian, and Guy A. Rouleau
- Subjects
Adult ,Male ,medicine.medical_specialty ,Reference Values ,RNA analysis ,Medicine ,Humans ,Atrioventricular Block ,Aged ,Gynecology ,business.industry ,Amino acid substitution ,General Medicine ,DNA ,Middle Aged ,Lamin Type A ,Pedigree ,Alternative Splicing ,Neurology ,Amino Acid Substitution ,Muscular Dystrophies, Limb-Girdle ,Reference values ,Case-Control Studies ,French canadian ,RNA ,Female ,Neurology (clinical) ,business ,Novel mutation - Abstract
Background:Limb girdle muscular dystrophy type 1B is an autosomal dominant disease characterized by late onset proximal muscle involvement associated with cardiac complications such as atrioventricular conduction blocks, dilated cardiomyopathy, and sudden death.Objective:Define the full phenotypic spectrum of a new mutation in the LMNA gene causing limb girdle muscular dystrophy type 1B.Methods:We identified a large French Canadian family with the LGMD 1B phenotype and a cardiac conduction disease phenotype that carried a new mutation in the LMNA gene and sought to define its full phenotypic spectrum by performing complete neurological and cardiac evaluations, muscle biopsy, RNA and DNA studies.Results:The proband and 12 living at risk relatives were tested. In total, we identified seven carriers of a new (IVS9-3C>G) LMNA gene mutation. Of the three symptomatic patients, all had cardiac involvement, but only two presented proximal limb weakness. The one available muscle biopsy demonstrated a normally expressed lamin A/C protein, localized at the nuclear envelope. RNA study revealed a loss of exon 10 transcription caused by the IVS9-3C to G splicing mutation.Conclusions:We have identified a new mutations in the LMNA gene in a French-Canadian family. This diagnosis has important implications for affected patients and their siblings since they may eventually require pacemaker implantation.
- Published
- 2008
30. Clinical and genetic study of autosomal recessive cerebellar ataxia type 1
- Author
-
Jean-Pierre Bouchard, Guy A. Rouleau, Denis Brunet, Steve Verreault, Nicolas Chrestian, Nicolas Dupré, François Gros-Louis, Bernard Brais, and Danielle de Verteuil
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Ataxia ,Cerebellar Ataxia ,Population ,DNA Mutational Analysis ,Nerve Tissue Proteins ,medicine ,Humans ,Oculomotor apraxia ,Age of Onset ,education ,Aged ,Genetics ,Family Health ,education.field_of_study ,Cerebellar ataxia ,Genetic heterogeneity ,business.industry ,Abetalipoproteinemia ,Nuclear Proteins ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Cytoskeletal Proteins ,Neurology ,Ataxia-telangiectasia ,Mutation ,Cerebellar atrophy ,Female ,Neurology (clinical) ,medicine.symptom ,business - Abstract
Objective: Define the phenotype and genotype of a cluster of families with a relatively pure cerebellar ataxia referred to as autosomal recessive cerebellar ataxia type 1 (ARCA-1). Methods: We ascertained 64 probands and affected members of 30 French-Canadian families all showing similar clinical features and originating from the same region of Quebec. After informed consent, we performed detailed clinical history, neurological examination, brain imaging, nerve conduction studies, and SYNE1 mutation detection of all available subjects. Results: Based on the cases examined, ARCA-1 is a cerebellar syndrome characterized by recessive transmission, middle-age onset (mean, 31.60; range, 17– 46 years), slow progression and moderate disability, significant dysarthria, mild oculomotor abnormalities, occasional brisk reflexes in the lower extremities, normal nerve conduction studies, and diffuse cerebellar atrophy on imaging. We identified a total of seven mutations in our population, thereby providing evidence of genotypic heterogeneity. Patients with different mutations did not show significant phenotypic heterogeneity. Interpretation: We identified a cluster of French-Canadian families with a new recessive ataxia of relatively pure cerebellar type caused by mutations in SYNE1. The function of SYNE1 is thus critical in the maintenance of cerebellar structure in humans. We expect that this disease will be a common cause of middle-age-onset recessive ataxia worldwide. Ann Neurol 2007;62:93–98 The hereditary ataxias can be divided based on their mode of inheritance into autosomal dominant, autosomal recessive, X-linked, and mitochondrial ataxias. These disease categories share the prototypic feature of impaired walking, although they usually present a variety of other neurological symptoms such as pyramidal signs, peripheral neuropathy, extrapyramidal signs, cognitive loss, or retinopathy. The autosomal recessive ataxias are also a heterogeneous group of disorders composed mainly of Friedreich’s ataxia, ataxia telangiectasia, ataxia with vitamin E deficiency, autosomal recessive spastic ataxia of Charlevoix–Saguenay (ARSACS), abetalipoproteinemia, and ataxia with oculomotor apraxia types 1 and 2. 1 Over the past decade, we have identified a large cluster of French-Canadian families whose ancestors originate mostly from the same region of the Province of Quebec in Canada. This region, located in southeastern Quebec near the US border, is called Beauce. The affected individuals in these families all share similar clinical characteristics that define this new disease entity we named ARCA-1, also known as recessive ataxia of Beauce. 2,3 Genome-wide linkage and fine-mapping
- Published
- 2007
31. Hereditary neuropathy with liability to pressure palsies in childhood: case series and update from the literature
- Author
-
Jiri Vajsar, Craig Campbell, Chantal Poulin, Hugh J. McMillan, and Nicolas Chrestian
- Subjects
Pediatrics ,medicine.medical_specialty ,Neurology ,Series (mathematics) ,business.industry ,Liability ,Medicine ,Neurology (clinical) ,General Medicine ,business - Abstract
Introduction: HNPP presentation in childhood is rare and diverse and most of the published literature is based on case reports. Materials and Methods: we analyzed the data of 11 children with deletion in PMP22 gene, reviewed the published reports of HNPP in children and compared our data with the reports from the literature review. Results: Peroneal palsy was the most common presentation (50%) followed by the brachial plexus palsy in 30% of cases. The trigger of the demyelinating event was identified only in 27%. 72% of our cohort developed only one acute episode of nerve palsy. Nerve conduction studies were always suggestive of the diagnosis demonstrating 60% of cases a polyneuropathy, 50% of cases conduction block but 100% of bilateral or unilateral electrophysiologic entrapment of the median nerve at the carpal tunnel. Conclusion: The clinical presentation of HNPP in childhood is heterogeneous and EMG findings are abnormal. Any unexplained mononeuropathy or multifocal neuropathy should lead to PMP22 gene testing to look for the deletion. Early diagnosis is important for the genetic counselling but also for the appropriate care of these patients.
- Published
- 2015
32. Myotonia congenita--a cause of muscle weakness and stiffness
- Author
-
Nicolas Chrestian, Jack Puymirat, Jean-Pierre Bouchard, and Nicolas Dupré
- Subjects
musculoskeletal diseases ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Weakness ,Myotonia Congenita ,Neurological examination ,Genes, Recessive ,Mexiletine ,Diagnosis, Differential ,Cellular and Molecular Neuroscience ,Medicine ,Humans ,Muscle, Skeletal ,Neurologic Examination ,Muscle biopsy ,Muscle Weakness ,medicine.diagnostic_test ,business.industry ,Myotonia congenita ,Electromyography ,Dystrophy ,Muscle weakness ,Middle Aged ,medicine.disease ,Myotonia ,Dermatology ,nervous system diseases ,Surgery ,Female ,Neurology (clinical) ,medicine.symptom ,business ,medicine.drug - Abstract
Background A 56-year-old woman was referred to a neurogenetic clinic with a history of stiffness and transient weakness. A previous needle electromyogram had confirmed the presence of myotonia, but a muscle biopsy had revealed no evidence of dystrophy. Investigations Neurological examination, electrophysiological studies and genetic testing. Diagnosis Recessive myotonia congenita (Becker's disease). Management Explanation of the nature of the disease and treatment with mexiletine 200 mg twice daily.
- Published
- 2006
33. G.P.18.08 Clinical and genetic study of autosomal recessive cerebellar ataxia type 1
- Author
-
Nicolas Dupré, D. de Verteuil, J.P. Bouchard, Guy A. Rouleau, François Gros-Louis, Nicolas Chrestian, and Bernard Brais
- Subjects
Genetics ,Neurology ,Pediatrics, Perinatology and Child Health ,Neurology (clinical) ,Autosomal Recessive Cerebellar Ataxia Type 1 ,Biology ,Genetics (clinical) - Published
- 2007
34. G.P.10.15 Genotype–phenotype correlation and identification of new mutations in non-dystrophic myotonias
- Author
-
Nicolas Chrestian, J.P. Bouchard, Denis Brunet, J. Mathieu, Nicolas Dupré, and Jack Puymirat
- Subjects
Correlation ,Genetics ,Neurology ,Pediatrics, Perinatology and Child Health ,Identification (biology) ,Neurology (clinical) ,Biology ,Genetics (clinical) ,Genotype phenotype - Published
- 2007
35. G.P.5.05 A novel mutation in a French–Canadian family with LGMD1B
- Author
-
Peter Gould, Paul N. Valdmanis, Jean Champagne, Najmeddine Echahidi, Nicolas Chrestian, Nicolas Dupré, Denis Brunet, and Guy A. Rouleau
- Subjects
Genetics ,History ,Neurology ,Pediatrics, Perinatology and Child Health ,French canadian ,Neurology (clinical) ,Novel mutation ,Genetics (clinical) - Published
- 2007
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.