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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorCRUZ, Pedro M. Rodriguez
dc.contributor.authorCOSSINS, Judith
dc.contributor.authorESTEPHAN, Eduardo de Paula
dc.contributor.authorMUNELL, Francina
dc.contributor.authorSELBY, Kathryn
dc.contributor.authorHIRANO, Michio
dc.contributor.authorMAROOFIN, Reza
dc.contributor.authorMEHRJARDI, Mohammad Yahya Vahidi
dc.contributor.authorCHOW, Gabriel
dc.contributor.authorCARR, Aisling
dc.contributor.authorMANZUR, Adnan
dc.contributor.authorROBB, Stephanie
dc.contributor.authorMUNOT, Pinki
dc.contributor.authorLIU, Wei Wei
dc.contributor.authorBANKA, Siddharth
dc.contributor.authorFRASER, Harry
dc.contributor.authorGOEDE, Christian De
dc.contributor.authorZANOTELI, Edmar
dc.contributor.authorREED, Umbertina Conti
dc.contributor.authorSAGE, Abigail
dc.contributor.authorGRATACOS, Margarida
dc.contributor.authorMACAYA, Alfons
dc.contributor.authorDUSL, Marina
dc.contributor.authorSENDEREK, Jan
dc.contributor.authorTOPF, Ana
dc.contributor.authorHOFER, Monika
dc.contributor.authorKNIGHT, Ravi
dc.contributor.authorRAMDAS, Sithara
dc.contributor.authorJAYAWANT, Sandeep
dc.contributor.authorLOCHMUELLER, Hans
dc.contributor.authorPALACE, Jacqueline
dc.contributor.authorBEESON, David
dc.date.accessioned2019-09-23T14:18:45Z-
dc.date.available2019-09-23T14:18:45Z-
dc.date.issued2019
dc.identifier.citationBRAIN, v.142, p.1547-1560, 2019
dc.identifier.issn0006-8950
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/33503-
dc.description.abstractNext generation sequencing techniques were recently used to show mutations in COL13A1 cause synaptic basal lamina-associated congenital myasthenic syndrome type 19. Animal studies showed COL13A1, a synaptic extracellular-matrix protein, is involved in the formation and maintenance of the neuromuscular synapse that appears independent of the Agrin-LRP4-MuSK-DOK7 acetylcholine receptor clustering pathway. Here, we report the phenotypic spectrum of 16 patients from 11 kinships harbouring homozygous or heteroallelic mutations in COL13A1. Clinical presentation was mostly at birth with hypotonia and breathing and feeding difficulties often requiring ventilation and artificial feeding. Respiratory crisis related to recurrent apnoeas, sometimes triggered by chest infections, were common early in life but resolved over time. The predominant pattern of muscle weakness included bilateral ptosis (non-fatigable in adulthood), myopathic facies and marked axial weakness, especially of neck flexion, while limb muscles were less involved. Other features included facial dysmorphism, skeletal abnormalities and mild learning difficulties. All patients tested had results consistent with abnormal neuromuscular transmission. Muscle biopsies were within normal limits or showed non-specific changes. Muscle MRI and serum creatine kinase levels were normal. In keeping with COL13A1 mutations affecting both synaptic structure and presynaptic function, treatment with 3,4-diaminopyridine and salbutamol resulted in motor and respiratory function improvement. In non-treated cases, disease severity and muscle strength improved gradually over time and several adults recovered normal muscle strength in the limbs. In summary, patients with COL13A1 mutations present mostly with severe early-onset myasthenic syndrome with feeding and breathing difficulties. Axial weakness is greater than limb weakness. Disease course improves gradually over time, which could be consistent with the less prominent role of COL13A1 once the neuromuscular junction is mature. This report emphasizes the role of collagens at the human muscle endplate and should facilitate the recognition of this disorder, which can benefit from pharmacological treatment.eng
dc.description.sponsorshipUK NHS National Highly Specialised Service
dc.description.sponsorshipMRC Programme Grant [MR/M006824/1]
dc.description.sponsorshipUSP [PRPG 3/2017]
dc.language.isoeng
dc.publisherOXFORD UNIV PRESSeng
dc.relation.ispartofBrain
dc.rightsrestrictedAccesseng
dc.subjectcongenital myasthenic syndromeseng
dc.subjectCOL13A1eng
dc.subjectsynaptic basal laminaeng
dc.subjectsalbutamoleng
dc.subject3,4-diaminopyridineeng
dc.subject.otherking-denborough-syndromeeng
dc.subject.otherxiii collageneng
dc.subject.otherreceptoreng
dc.subject.otherinsensitivityeng
dc.subject.otherexpressioneng
dc.subject.othermaturationeng
dc.subject.otheranhidrosiseng
dc.subject.othergeneeng
dc.subject.otherpaineng
dc.titleThe clinical spectrum of the congenital myasthenic syndrome resulting from COL13A1 mutationseng
dc.typearticleeng
dc.rights.holderCopyright OXFORD UNIV PRESSeng
dc.identifier.doi10.1093/brain/awz107
dc.identifier.pmid31081514
dc.subject.wosClinical Neurologyeng
dc.subject.wosNeuroscienceseng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
hcfmusp.author.externalCRUZ, Pedro M. Rodriguez:Univ Oxford, Weatherall Inst Mol Med, Nuffield Dept Clin Neurosci, Neurosci Grp, Oxford OX3 9DS, England; Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Neurosci, Oxford OX3 9DU, England
hcfmusp.author.externalCOSSINS, Judith:Univ Oxford, Weatherall Inst Mol Med, Nuffield Dept Clin Neurosci, Neurosci Grp, Oxford OX3 9DS, England
hcfmusp.author.externalMUNELL, Francina:Hosp Univ Vall dHebron, Vall dHebron Res Inst VHIR, Child Neurol Unit, Neuromuscular Disorders Grp, Barcelona, Spain
hcfmusp.author.externalSELBY, Kathryn:Univ British Columbia, Vancouver, BC, Canada
hcfmusp.author.externalHIRANO, Michio:Columbia Univ, Dept Neurol, H Houston Merritt Neuromuscular Res Ctr, Med Ctr, New York, NY USA
hcfmusp.author.externalMAROOFIN, Reza:St Georges Univ London, Mol & Clin Sci Inst, Cranmer Terrace, London SW17 0RE, England
hcfmusp.author.externalMEHRJARDI, Mohammad Yahya Vahidi:Shahid Sadoughi Univ Med Sci, Med Genet Res Ctr, Yazd, Iran
hcfmusp.author.externalCHOW, Gabriel:Nottingham Univ Hosp NHS Trust, Nottingham City Hosp, Dept Paediat Neurol, Hucknall Rd, Nottingham NG5 1PB, England
hcfmusp.author.externalCARR, Aisling:Natl Hosp Neurol & Neurosurg, MRC Ctr Neuromuscular Dis, London WC1N 3BG, England
hcfmusp.author.externalMANZUR, Adnan:UCL Great Ormond St Inst Child Hlth, Dubowitz Neuromuscular Ctr, London WC1N 3JH, England; UCL Great Ormond St Inst Child Hlth, MRC Ctr Neuromuscular Dis, London WC1N 3JH, England
hcfmusp.author.externalROBB, Stephanie:UCL Great Ormond St Inst Child Hlth, Dubowitz Neuromuscular Ctr, London WC1N 3JH, England; UCL Great Ormond St Inst Child Hlth, MRC Ctr Neuromuscular Dis, London WC1N 3JH, England
hcfmusp.author.externalMUNOT, Pinki:UCL Great Ormond St Inst Child Hlth, Dubowitz Neuromuscular Ctr, London WC1N 3JH, England; UCL Great Ormond St Inst Child Hlth, MRC Ctr Neuromuscular Dis, London WC1N 3JH, England
hcfmusp.author.externalLIU, Wei Wei:Univ Oxford, Weatherall Inst Mol Med, Nuffield Dept Clin Neurosci, Neurosci Grp, Oxford OX3 9DS, England
hcfmusp.author.externalBANKA, Siddharth:Manchester Univ NHS Fdn Trust, St Marys Hosp, Manchester Ctr Genom Med, Hlth Innovat Manchester, Manchester M13 9WL, Lancs, England
hcfmusp.author.externalFRASER, Harry:Manchester Univ NHS Fdn Trust, St Marys Hosp, Manchester Ctr Genom Med, Hlth Innovat Manchester, Manchester M13 9WL, Lancs, England
hcfmusp.author.externalGOEDE, Christian De:Royal Preston Hosp, Dept Paediat Neurol, Preston PR2 9HT, Lancs, England
hcfmusp.author.externalSAGE, Abigail:Columbia Univ, Dept Neurol, H Houston Merritt Neuromuscular Res Ctr, Med Ctr, New York, NY USA
hcfmusp.author.externalGRATACOS, Margarida:Hosp Univ Vall dHebron, Dept Clin Neurophysiol, Barcelona, Spain
hcfmusp.author.externalMACAYA, Alfons:Hosp Univ Vall dHebron, Vall dHebron Res Inst VHIR, Child Neurol Unit, Neuromuscular Disorders Grp, Barcelona, Spain
hcfmusp.author.externalDUSL, Marina:Univ Hosp LMU Munich, Friedrich Baur Inst, Dept Neurol, Munich, Germany
hcfmusp.author.externalSENDEREK, Jan:Univ Hosp LMU Munich, Friedrich Baur Inst, Dept Neurol, Munich, Germany
hcfmusp.author.externalTOPF, Ana:Inst Genet Med, Cent Pkwy, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England
hcfmusp.author.externalHOFER, Monika:John Radcliffe Hosp NHS Fdn Trust, Dept Neuropathol, Oxford OX3 9DU, England
hcfmusp.author.externalKNIGHT, Ravi:John Radcliffe Hosp NHS Fdn Trust, Dept Clin Neurophysiol, Oxford OX3 9DU, England
hcfmusp.author.externalRAMDAS, Sithara:John Radcliffe Hosp NHS Fdn Trust, Dept Paediat Neurol, Oxford OX3 9DU, England
hcfmusp.author.externalJAYAWANT, Sandeep:John Radcliffe Hosp NHS Fdn Trust, Dept Paediat Neurol, Oxford OX3 9DU, England
hcfmusp.author.externalLOCHMUELLER, Hans:Univ Freiburg, Fac Med, Dept Neuropediat & Muscle Disorders, Med Ctr, Freiburg, Germany; Barcelona Inst Sci & Technol, Ctr Genom Regulat, Ctr Nacl Anal Genom CNAG CRG, Barcelona, Spain; Univ Ottawa, Childrens Hosp, Eastern Ontario Res Inst, Ottawa, ON, Canada; Ottawa Hosp, Dept Med, Div Neurol, Ottawa, ON, Canada
hcfmusp.author.externalPALACE, Jacqueline:Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Neurosci, Oxford OX3 9DU, England
hcfmusp.author.externalBEESON, David:Univ Oxford, Weatherall Inst Mol Med, Nuffield Dept Clin Neurosci, Neurosci Grp, Oxford OX3 9DS, England
hcfmusp.description.beginpage1547
hcfmusp.description.endpage1560
hcfmusp.description.volume142
hcfmusp.origemWOS
hcfmusp.origem.idWOS:000481419700016
hcfmusp.origem.id2-s2.0-85066964236
hcfmusp.publisher.cityOXFORDeng
hcfmusp.publisher.countryENGLANDeng
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dc.description.indexMEDLINEeng
dc.identifier.eissn1460-2156
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hcfmusp.scopus.lastupdate2022-06-10-
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