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Myasthenic syndromes in Turkish kinships due to mutations in the acetylcholine receptor
Author(s) -
Ohno Kinji,
Anlar Banu,
Özdirim Emire,
Brengman Joan M.,
DeBleecker Jan L.,
Engel Andrew G.
Publication year - 1998
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410440214
Subject(s) - mutation , genetics , biology , acetylcholine receptor , consanguinity , nonsense mutation , gene , splice , missense mutation , receptor
We report and functionally characterize five new mutations of the acetylcholine receptor (AChR) in 11 Turkish patients with recessive congenital myasthenic syndromes (CMS)s belonging to six families. All mutations are in the ε‐subunit gene. Parental consanguinity is present in three families. The disease cosegregates with homozygous mutations in five families and with two different heteroallelic mutations in one family. Four mutations are frameshifting, predicting truncation of the ε subunit, and one occurs at a splice donor site. Expression of each frameshifting mutation and the likely transcripts of the splice‐site mutation in human embryonic kidney 293 cells shows that each mutation is a null mutation. The findings support the notion that loss‐of7hyphen;function mutations of the acetylcholine receptor causing CMS are concentrated in the ε subunit, and that such mutations are a frequent cause of CMS.