Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital myasthenic syndromes comprise heterogeneous genetic diseases characterized by compromised neuromuscular transmission. Congenital myasthenic syndromes are classified as presynaptic, synaptic, or postsynaptic, depending on the primary defect's location within the neuromuscular junction. Presynaptic forms are the rarest, affecting an estimated 7-8% of patients; synaptic forms account for approximately 14-15% of patients; and the remaining 75-80% are attributable to postsynaptic defects. Clinical manifestations vary by congenital myasthenic syndrome subtype. Electrophysiologic, morphologic, and molecular descriptions of various forms of congenital myasthenic syndromes have led to an enhanced understanding of clinical manifestations and disease pathophysiology. Although congenital myasthenic syndromes are indicated by clinical manifestations, family history, electrophysiologic studies, and responses to acetylcholinesterase inhibitors, overlap in some presentations occurs. Therefore, genetic testing may be necessary to identify specific mutations in CHAT, COLQ, LAMB2, CHRNA, CHRNB, CHRND, CHRNE, CHRNG, RAPSN, DOK7, MUSK, AGRN, SCN4A, GFPT1, or PLEC1 genes. The identification of congenital myasthenic syndromes subtypes will prove important in the treatment of these patients. Different drugs may be beneficial, or should be avoided because they are ineffective or worsen some forms of congenital myasthenic syndromes. We explore the classification, clinical manifestations, electrophysiologic features, genetics, and treatment responses of each congenital myasthenic syndrome subtype.
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PMID:Congenital myasthenic syndrome: a brief review. 2235 87

The congenital myasthenic syndromes (CMS) are heterogeneous disorders in which the safety margin of neuromuscular transmission is compromised by one or more specific mechanisms. The disease proteins reside in the nerve terminal, the synaptic basal lamina, or in the postsynaptic region, or at multiple sites at the neuromuscular junction as well as in other tissues. Targeted mutation analysis by Sanger or exome sequencing has been facilitated by characteristic phenotypic features of some CMS. No fewer than 20 disease genes have been recognized to date. In one-half of the currently identified probands, the disease stems from mutations in genes encoding subunits of the muscle form of the acetylcholine receptor (CHRNA1, CHRNB, CHRNAD1, and CHRNE). In 10-14% of the probands the disease is caused by mutations in RAPSN, DOK 7, or COLQ, and in 5% by mutations in CHAT. Other less frequently identified disease genes include LAMB2, AGRN, LRP4, MUSK, GFPT1, DPAGT1, ALG2, and ALG 14 as well as SCN4A, PREPL, PLEC1, DNM2, and MTM1. Identification of the genetic basis of each CMS is important not only for genetic counseling and disease prevention but also for therapy, because therapeutic agents that benefit one type of CMS can be harmful in another.
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PMID:Genetic basis and phenotypic features of congenital myasthenic syndromes. 2947 1