Novel COLQ mutation 950delC in synaptic congenital myasthenic syndrome and symptomatic heterozygous relatives

Schreiner, Felix; Hoppenz, Marc; Klaeren, Ruth; Reimann, Jens; Woelfle, Joachim

doi:10.1016/j.nmd.2006.11.010

Cited by 13 publications

(14 citation statements)

References 10 publications

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“…Rarely, microcephaly has been reported [41]. Interestingly, heterozygote carriers can present with congenital ptosis [44]. Single nerve stimuli may evoke double responses.…”

Section: Resultsmentioning

confidence: 99%

Congenital myasthenic syndromes

Finsterer

2019

Orphanet J Rare Dis

146

154

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Objectives Congenital myasthenic syndromes (CMSs) are a genotypically and phenotypically heterogeneous group of neuromuscular disorders, which have in common an impaired neuromuscular transmission. Since the field of CMSs is steadily expanding, the present review aimed at summarizing and discussing current knowledge and recent advances concerning the etiology, clinical presentation, diagnosis, and treatment of CMSs. Methods Systematic literature review. Results Currently, mutations in 32 genes are made responsible for autosomal dominant or autosomal recessive CMSs. These mutations concern 8 presynaptic, 4 synaptic, 15 post-synaptic, and 5 glycosilation proteins. These proteins function as ion-channels, enzymes, or structural, signalling, sensor, or transporter proteins. The most common causative genes are CHAT, COLQ, RAPSN, CHRNE, DOK7, and GFPT1. Phenotypically, these mutations manifest as abnormal fatigability or permanent or fluctuating weakness of extra-ocular, facial, bulbar, axial, respiratory, or limb muscles, hypotonia, or developmental delay. Cognitive disability, dysmorphism, neuropathy, or epilepsy are rare. Low- or high-frequency repetitive nerve stimulation may show an abnormal increment or decrement, and SF-EMG an increased jitter or blockings. Most CMSs respond favourably to acetylcholine-esterase inhibitors, 3,4-diamino-pyridine, salbutamol, albuterol, ephedrine, fluoxetine, or atracurium. Conclusions CMSs are an increasingly recognised group of genetically transmitted defects, which usually respond favorably to drugs enhancing the neuromuscular transmission. CMSs need to be differentiated from neuromuscular disorders due to muscle or nerve dysfunction.

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“…Rarely, microcephaly has been reported [41]. Interestingly, heterozygote carriers can present with congenital ptosis [44]. Single nerve stimuli may evoke double responses.…”

Section: Resultsmentioning

confidence: 99%

Congenital myasthenic syndromes

Finsterer

2019

Orphanet J Rare Dis

146

154

View full text Add to dashboard Cite

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“…ColQ deficiency brings to a drastically decreased AChE localization at NMJs (Feng et al, 1999), causing congenital myasthenic syndrome with AChE deficiency (Donger et al, 1998; Ohno et al, 1998, 2013; Schreiner et al, 2007). However, despite its cholinergic role, AChE-ColQ exerts multifunctional roles thanks to the ability of ColQ to binds several partners.…”

Section: Ache-colq Complex At the Nmjmentioning

confidence: 99%

Neuromuscular Junction Impairment in Amyotrophic Lateral Sclerosis: Reassessing the Role of Acetylcholinesterase

Campanari

García‐Ayllón

Ciura

et al. 2016

Front. Mol. Neurosci.

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Amyotrophic Lateral Sclerosis (ALS) is a highly debilitating disease caused by progressive degeneration of motorneurons (MNs). Due to the wide variety of genes and mutations identified in ALS, a highly varied etiology could ultimately converge to produce similar clinical symptoms. A major hypothesis in ALS research is the “distal axonopathy” with pathological changes occurring at the neuromuscular junction (NMJ), at very early stages of the disease, prior to MNs degeneration and onset of clinical symptoms. The NMJ is a highly specialized cholinergic synapse, allowing signaling between muscle and nerve necessary for skeletal muscle function. This nerve-muscle contact is characterized by the clustering of the collagen-tailed form of acetylcholinesterase (ColQ-AChE), together with other components of the extracellular matrix (ECM) and specific key molecules in the NMJ formation. Interestingly, in addition to their cholinergic role AChE is thought to play several “non-classical” roles that do not require catalytic function, most prominent among these is the facilitation of neurite growth, NMJ formation and survival. In all this context, abnormalities of AChE content have been found in plasma of ALS patients, in which AChE changes may reflect the neuromuscular disruption. We review these findings and particularly the evidences of changes of AChE at neuromuscular synapse in the pre-symptomatic stages of ALS.

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“…Agrin and ColQ are both present in the synaptic cleft and are therefore accessible to autoantibodies in vivo . Moreover, mutations that cause congenital myasthenia syndromes (CMS) have been found in both of these proteins, 25–31 and we therefore hypothesized that antibodies against either protein could potentially cause a disturbance of neuromuscular transmission. A schematic diagram showing the location of these and other key proteins at the NMJ is shown in Figure 1.…”

Section: Other Potential Antigenic Targetsmentioning

confidence: 99%

The search for new antigenic targets in myasthenia gravis

Cossins

Belaya

Zoltowska

et al. 2012

Annals of the New York Academy of Sciences

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Around 80% of myasthenia gravis patients have antibodies against the acetylcholine receptor, and 0-60% of the remaining patients have antibodies against the muscle-specific tyrosine kinase, MuSK. Another recently identified antigen is low-density lipoprotein receptor-related protein 4 (Lrp4). To improve the existing assays and widen the search for new antigenic targets, we have employed cell-based assays in which candidate target proteins are expressed on the cell surface of transfected cells and probed with patient sera. These assays, combined with use of myotube cultures to explore the effects of the antibodies, enable us to begin to identify new antigenic targets and test antibody pathogenicity in vitro.

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Novel COLQ mutation 950delC in synaptic congenital myasthenic syndrome and symptomatic heterozygous relatives

Cited by 13 publications

References 10 publications

Congenital myasthenic syndromes

Congenital myasthenic syndromes

Neuromuscular Junction Impairment in Amyotrophic Lateral Sclerosis: Reassessing the Role of Acetylcholinesterase

The search for new antigenic targets in myasthenia gravis

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