Clinical and molecular genetic findings in COLQ-mutant congenital myasthenic syndromes

التفاصيل البيبلوغرافية
العنوان: Clinical and molecular genetic findings in COLQ-mutant congenital myasthenic syndromes
المؤلفون: Friederike Hoellen, Gerhard Kurlemann, Agnes Herczegfalvi, Mohammad M. Kabiraj, Enrico Bertini, Juan J. Vílchez, Mustafa A. Salih, Adele D'Amico, Joachim Wölfle, Angela Abicht, Dana Siskova, Vedrana Milic Rasic, Jaume Colomer, Katarina Fabriciova, Juliane S. Müller, Ulrike Schara, Hanns Lochmüller, V. Mihaylova, Felix Schreiner, Bernhard Weschke, Rosana Herminia Scola
المصدر: Brain. 131:747-759
بيانات النشر: Oxford University Press (OUP), 2008.
سنة النشر: 2008
مصطلحات موضوعية: Male, Pathology, medicine.medical_specialty, Adolescent, Eye Movements, Genotype, Biopsy, Medizin, Neuromuscular transmission, Action Potentials, Muscle Proteins, Angiotensin-Converting Enzyme Inhibitors, Bioinformatics, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, COLQ, medicine, Humans, CHRNE, Age of Onset, Child, Muscle, Skeletal, 030304 developmental biology, Myasthenic Syndromes, Congenital, 0303 health sciences, biology, Infant, Newborn, Genetic disorder, Infant, Congenital myasthenic syndrome, medicine.disease, Acetylcholinesterase, Electric Stimulation, Myasthenia gravis, 3. Good health, Phenotype, Treatment Outcome, chemistry, Child, Preschool, Mutation, biology.protein, Female, Collagen, Neurology (clinical), Esterase inhibitor, 030217 neurology & neurosurgery
الوصف: Congenital myasthenic syndromes (CMS) are clinically and genetically heterogeneous inherited disorders characterized by impaired neuromuscular transmission. Mutations in the acetylcholinesterase (AChE) collagen-like tail subunit gene (COLQ) cause synaptic basal-lamina associated CMS with end-plate AChE deficiency. Here we present the clinical and molecular genetic findings of 22 COLQ-mutant CMS patients, carrying a total of 20 different COLQ mutations, 11 of them had not previously been reported. Typically, patients with esterase deficiency suffer from a severe, progressive weakness with onset at birth or in early infancy. In addition, patients with a late onset showing a mild course of disease are described. AChE inhibitor therapy, beneficial for other forms of CMS, is of no effect in cases of esterase deficiency. The large cohort of COLQ patients studied here enabled us to define additional clinical presentations associated with COLQ mutations that differ from the 'classical' phenotypes: several patients with disease onset at birth or in early infancy presented an unexpected, mild disease course without significant progression of weakness. Moreover, many patients had clinical features reminiscent of limb-girdle CMS with mutations in the recently discovered DOK7 gene, including sparing of eye movements and a predominantly proximal muscle weakness. There was no long-term objective benefit from esterase inhibitors treatment in COLQ patients. Surprisingly, a short-term beneficial effect was observed in four patients and a Tensilon test was positive in two. Treatment with ephedrine was efficient in all five cases where it was administered. The variability of phenotypes caused by COLQ mutations, the divergence from the previously published classical clinical features and an initial positive response to esterase inhibitors in some patients may obscure AChE deficiency as the molecular cause of the disease and delay the start of appropriate therapy. Moreover, overlap with other CMS subtypes and potentially absence of a repetitive compound muscle action potential should be considered in the diagnosis of COLQ-mutated patients.
تدمد: 1460-2156
0006-8950
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7c9eae3970323ff8f8f2325160399063Test
https://doi.org/10.1093/brain/awm325Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....7c9eae3970323ff8f8f2325160399063
قاعدة البيانات: OpenAIRE