title: Congenital myasthenic syndrome in Israel: Genetic and clinical characterization.
abstract: The objective of the study was to evaluate the epidemiology of patients with congenital myasthenic syndrome (CMS) in Israel. Targeted mutation analysis was performed based on the clinical symptoms and electrophysiological findings for known CMS. Additional specific tests were performed in patients of Iranian and/or Iraqi Jewish origin. All medical records were reviewed and clinical data, genetic mutations and outcomes were recorded. Forty-five patients with genetic mutations in known CMS genes from 35 families were identified. Mutations in RAPSN were identified in 13 kinships in Israel. The most common mutation was c.-38A>G detected in 8 patients of Iranian and/or Iraqi Jewish origin. Four different recessive mutations in COLQ were identified in 11 kinships, 10 of which were of Muslim-Arab descent. Mutations in CHRNE were identified in 7 kinships. Less commonly detected mutations were in CHRND, CHAT, GFPT1 and DOK7. In conclusion, mutations in RAPSN and COLQ are the most common causes of CMS in our cohort. Specific mutations in COLQ, RAPSN, and CHRNE occur in specific ethnic populations and should be taken into account when the diagnosis of a CMS is suspected.
authors.affiliation: Institute of Child Neurology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: aharonis@zahav.net.il.
authors.forename: Sharon
authors.initials: S
authors.lastname: Aharoni
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Neurology, Wolfson Medical Center, Holon, Israel.
authors.forename: Menachem
authors.initials: M
authors.lastname: Sadeh
authors.affiliation: Neuropediatric Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Shapira
authors.affiliation: Neuropediatric Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Simon
authors.initials: S
authors.lastname: Edvardson
authors.affiliation: Neuropediatric Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Muhannad
authors.initials: M
authors.lastname: Daana
authors.affiliation: Neuropediatric Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Talia
authors.initials: T
authors.lastname: Dor-Wollman
authors.affiliation: Pediatric Neurology and Developmental Unit, Loewenstein Rehabilitation Hospital, Raanana, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Aviva
authors.initials: A
authors.lastname: Mimouni-Bloch
authors.affiliation: Institute of Child Neurology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Halevy
authors.affiliation: Institute of Child Neurology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Rony
authors.initials: R
authors.lastname: Cohen
authors.affiliation: Pediatric Neurology Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Liora
authors.initials: L
authors.lastname: Sagie
authors.affiliation: Department of Neurology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Zohar
authors.initials: Z
authors.lastname: Argov
authors.affiliation: Institute of Child Neurology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Rabie
authors.affiliation: Genetic Institute, Emek Medical Center, Afula, Israel.
authors.forename: Ronen
authors.initials: R
authors.lastname: Spiegel
authors.affiliation: Genetic Institute, Emek Medical Center, Afula, Israel.
authors.forename: Ilana
authors.initials: I
authors.lastname: Chervinsky
authors.affiliation: Genetics Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Naama
authors.initials: N
authors.lastname: Orenstein
authors.affiliation: Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN, USA.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Engel
authors.affiliation: Institute of Child Neurology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Nevo
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics*; D003094:Collagen / Q000235:genetics*; D004252:DNA Mutational Analysis; D006801:Humans; D007492:Iran / Q000208:ethnology; D007493:Iraq / Q000208:ethnology; D007557:Israel / Q000208:ethnology; D009124:Muscle Proteins / Q000235:genetics*; D020294:Myasthenic Syndromes, Congenital / Q000208:ethnology* / Q000235:genetics*; D010375:Pedigree; D011978:Receptors, Nicotinic / Q000235:genetics*
chemical_list: C504423:CHRNE protein, human; D009124:Muscle Proteins; D011978:Receptors, Nicotinic; C051609:peripheral membrane protein 43K; D003094:Collagen; D000110:Acetylcholinesterase; C114027:COLQ protein, human
keywords: CHRNE; COLQ; Congenital myasthenic syndrome (CMS); Genetic mutations; RAPSN