Congenital myasthenic syndromes

Hantaı̈, Daniel; Nicole, Sophie; Eymard, B.

doi:10.1097/wco.0b013e328364dc0f

Cited by 40 publications

(26 citation statements)

References 63 publications

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“…6 Depending on the localization of the mutated protein, CMSs are classified into four categories: (i) presynaptic compartment CMS, (ii) synaptic basal laminaassociated CMS, (iii) postsynaptic compartment CMS, and (iv) CMS caused by deficient protein glycosylation. Postsynaptic disorders can be divided into two kinetic defects, fast-channel (OMIM 608930) and slow-channel (OMIM 601462) CMSs, and a third disorder, CMS with acetylcholine receptor deficiency (OMIM 608931).…”

Section: Congenital Myasthenic Syndromesmentioning

confidence: 99%

“…Treatment consists of long-acting open-channel blockers fluoxetine and quinidine; however, the efficacy and tolerability features of these medications are limited. 6 In fast-channel CMSs, receptor activations are brief because acetylcholine receptors do not stay open long enough. These are usually caused by loss-of-function mutations and follow autosomal recessive inheritance.…”

Section: Congenital Myasthenic Syndromesmentioning

confidence: 99%

“…Fast-channel CMS is treated with acetylcholine esterase inhibitors and 3,4-diaminopyridine. 6 The most common type of CMS, i.e., CMS associated with acetylcholine receptor deficiency, may or may not have minor kinetic abnormalities. The causative mutations involve loss of function, and the inheritance pattern is autosomal recessive.…”

Section: Congenital Myasthenic Syndromesmentioning

confidence: 99%

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Nicotinic acetylcholine receptors in human genetic disease

Schaaf

2014

Genetics in Medicine

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Section: Congenital Myasthenic Syndromesmentioning

confidence: 99%

Section: Congenital Myasthenic Syndromesmentioning

confidence: 99%

Section: Congenital Myasthenic Syndromesmentioning

confidence: 99%

See 1 more Smart Citation

Nicotinic acetylcholine receptors in human genetic disease

Schaaf

2014

Genetics in Medicine

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“…Präsynaptische, synaptische oder postsynaptische Defekte führen zu einer abnorm gesteigerten oder abgeschwächten Antwort an der motorischen Endplatte 28,32,39 .…”

Section: Zusammenfassungunclassified

33.3 Kongenitale myasthene Syndrome

Grehl¹,

Reinhardt²

2013

Checkliste Neurologie

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“…For instance, the study by Maselli et al (2009) demonstrated mutations in laminin-β2 are responsible for a severe form of CMS, which is a neuromuscular disorder characterised by muscle weakness resulting from defects at the NMJ and weakened neurotransmission (Hantai et al, 2004;Engel & Sine, 2005;Maselli et al, 2012).…”

Section: Rationalementioning

confidence: 99%

The role of synaptic laminins-α4 and -β2 in maturation and maintenance of the neuromuscular synapse

Lee¹

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The proper development, maturation and maintenance of the neuromuscular junction (NMJ) are critical for ensuring efficient neurotransmission. Proteins found within the basal lamina of the synaptic cleft, namely the laminins family, are heavily involved in maintaining normal structure and function of the NMJ. In particular, individual laminin chains such as laminin-β2, -α4 and -α5 play essential roles in organisation and maintenance of the NMJ. These laminin chains interact together to form three synapse specific laminin heterotrimers; laminin-221 (α2β2γ1), laminin-421 (α4β2γ1) and laminin-521 (α5β2γ1).Laminin-β2 is the common laminin chain found in each of these synapse specific laminin heterotrimers. In-vitro it has been shown to play a key role in the organisation of the presynaptic elements at the NMJ via its interaction and clustering of the N-and P/Q-type voltage-gated calciums (VGCCs). During development of the NMJ, both N-and P/Q-type VGCCs are involved in mediating neurotransmitter release. As the NMJ matures, P/Q-type becomes the dominant channel involved in release while N-type takes on the role of fine-tuning calcium influx. Laminin-α4, on the other hand, ensures proper alignment of presynaptic active zones to postjunctional folds at the NMJ, with its loss resulting in misalignment of these specialisations. Furthermore, this laminin chain has been shown to be involved in the maintenance of the NMJ with the observation of premature ageing features at 6 months of age (6MO) in laminin-α4 deficient mice (lama4 NMJs.In conclusion, this thesis has identified the significant roles laminins-α4 and -β2 play at the NMJ during development, maturation and maintenance. Results suggest that laminin-β2 is not only an important regulator of the presynaptic maturation through the switching of VGCCs and clustering of P/Q-type VGCCs, but also equally important for maturation of the postsynaptic apparatus. Ipropose that laminin-β2 is important for the maturation of each component at the NMJ. The altered responses in transmission properties presented by aged wild-type NMJs which resembled adult lama4 -/-, preceded by altered expression of laminin-α4 chain, strongly suggest that laminin-α4 is not only important for maintaining proper alignment of pre-to postsynaptic NMJ, but also essentially important for maintaining a healthy adult NMJ. Finally, I observed early alterations in expression of laminin-α4 at the NMJs in diseased mouse model of ALS prior to any appearance of neuromotor impairment, suggesting a potential involvement of laminins in NMJ degeneration associated with neuromuscular disorders such as ALS.ii

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Congenital myasthenic syndromes

Cited by 40 publications

References 63 publications

Nicotinic acetylcholine receptors in human genetic disease

Nicotinic acetylcholine receptors in human genetic disease

33.3 Kongenitale myasthene Syndrome

The role of synaptic laminins-α4 and -β2 in maturation and maintenance of the neuromuscular synapse

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