title: Mutations in the embryonal subunit of the acetylcholine receptor (CHRNG) cause lethal and Escobar variants of multiple pterygium syndrome.
abstract: Multiple pterygium syndromes (MPSs) comprise a group of multiple-congenital-anomaly disorders characterized by webbing (pterygia) of the neck, elbows, and/or knees and joint contractures (arthrogryposis). In addition, a variety of developmental defects (e.g., vertebral anomalies) may occur. MPSs are phenotypically and genetically heterogeneous but are traditionally divided into prenatally lethal and nonlethal (Escobar) types. To elucidate the pathogenesis of MPS, we undertook a genomewide linkage scan of a large consanguineous family and mapped a locus to 2q36-37. We then identified germline-inactivating mutations in the embryonal acetylcholine receptor gamma subunit (CHRNG) in families with both lethal and nonlethal MPSs. These findings extend the role of acetylcholine receptor dysfunction in human disease and provide new insights into the pathogenesis and management of fetal akinesia syndromes.
authors.affiliation: Section of Medical and Molecular Genetics, University of Birmingham, Institute of Biomedical Research, Edgbaston, Birmingham, B15 2TT, UK.
authors.forename: Neil V
authors.initials: NV
authors.lastname: Morgan
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brueton
authors.forename: Phillip
authors.initials: P
authors.lastname: Cox
authors.forename: Marie T
authors.initials: MT
authors.lastname: Greally
authors.forename: John
authors.initials: J
authors.lastname: Tolmie
authors.forename: Shanaz
authors.initials: S
authors.lastname: Pasha
authors.forename: Irene A
authors.initials: IA
authors.lastname: Aligianis
authors.forename: Hans
authors.initials: H
authors.lastname: van Bokhoven
authors.forename: Tamas
authors.initials: T
authors.lastname: Marton
authors.forename: Lihadh
authors.initials: L
authors.lastname: Al-Gazali
authors.forename: Jenny E V
authors.initials: JE
authors.lastname: Morton
authors.forename: Christine
authors.initials: C
authors.lastname: Oley
authors.forename: Colin A
authors.initials: CA
authors.lastname: Johnson
authors.forename: Richard C
authors.initials: RC
authors.lastname: Trembath
authors.forename: Han G
authors.initials: HG
authors.lastname: Brunner
authors.forename: Eamonn R
authors.initials: ER
authors.lastname: Maher
mesh_terms: D000015:Abnormalities, Multiple / Q000196:embryology / Q000235:genetics*; D000293:Adolescent; D002889:Chromosomes, Human, Pair 2; D005260:Female; D005333:Fetus / Q000002:abnormalities*; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D008297:Male; D010375:Pedigree; D021122:Protein Subunits / Q000235:genetics*; D011950:Receptors, Cholinergic / Q000235:genetics*; D013577:Syndrome
chemical_list: D021122:Protein Subunits; D011950:Receptors, Cholinergic