Subject(s)
Macular Degeneration/surgery , Pigment Epithelium of Eye/cytology , Retinal Detachment/surgery , Vitrectomy , Cell Division/physiology , Cell Survival/physiology , Cell Transplantation , Cells, Cultured , Humans , Pigment Epithelium of Eye/physiology , Pigment Epithelium of Eye/transplantationABSTRACT
The objective was to define the molecular mechanisms underlying congenital myasthenic syndromes (CMS) by studying mutations within genes encoding the acetylcholine receptor (AChR) and related proteins at the neuromuscular junction. It was found that mutations within muscle AChRs are the most common cause of CMS. The majority are located within the epsilon-subunit gene and result in AChR deficiency.
Subject(s)
Mutation , Myasthenic Syndromes, Congenital/genetics , Neuromuscular Junction/abnormalities , Receptors, Cholinergic/chemistry , Alleles , Animals , Cell Line , DNA Mutational Analysis , Exons , Extracellular Space/genetics , Extracellular Space/metabolism , Female , Humans , In Situ Hybridization/methods , Male , Myasthenic Syndromes, Congenital/classification , Myasthenic Syndromes, Congenital/diagnosis , Myasthenic Syndromes, Congenital/physiopathology , Neuromuscular Junction/genetics , Neuromuscular Junction/metabolism , Patch-Clamp Techniques , Polymorphism, Single-Stranded Conformational , Protein Structure, Secondary , Protein Subunits/genetics , Protein Subunits/metabolism , Receptors, Cholinergic/deficiency , Receptors, Cholinergic/genetics , Receptors, Cholinergic/physiology , Reverse Transcriptase Polymerase Chain Reaction , TransfectionABSTRACT
A reduction in the number of acetylcholine receptors (AChR) on the postsynaptic membrane is characteristic of MG. This may be inherited (AChR deficiency syndrome) or acquired (MG). The authors report two sisters with AChR deficiency caused by heteroallelic mutations in the AChR epsilon-subunit gene. The younger sister developed MG at 34 years. This unusual case raises the possibility that genetic defects of the AChR might be a factor in the etiology of autoimmune MG.
