Mutations in the embryonal subunit of the acetylcholine receptor (CHRNG) cause lethal and Escobar variants of multiple pterygium syndrome.
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.
Morgan
Neil V
NV
Section of Medical and Molecular Genetics, University of Birmingham, Institute of Biomedical Research, Edgbaston, Birmingham, B15 2TT, UK.
Brueton
Louise A
LA
Cox
Phillip
P
Greally
Marie T
MT
Tolmie
John
J
Pasha
Shanaz
S
Aligianis
Irene A
IA
van Bokhoven
Hans
H
Marton
Tamas
T
Al-Gazali
Lihadh
L
Morton
Jenny E V
JE
Oley
Christine
C
Johnson
Colin A
CA
Trembath
Richard C
RC
Brunner
Han G
HG
Maher
Eamonn R
ER
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
D021122:Protein Subunits; D011950:Receptors, Cholinergic