Mutations in the Embryonal Subunit of the Acetylcholine Receptor ( CHRNG) Cause Lethal and Escobar Variants of Multiple Pterygium Syndrome

• Published in: American journal of human genetics Vol. 79; no. 2; pp. 390 - 395
• Main Authors: Morgan, Neil V., Brueton, Louise A., Cox, Phillip, Greally, Marie T., Tolmie, John, Pasha, Shanaz, Aligianis, Irene A., van Bokhoven, Hans, Marton, Tamas, Al-Gazali, Lihadh, Morton, Jenny E.V., Oley, Christine, Johnson, Colin A., Trembath, Richard C., Brunner, Han G., Maher, Eamonn R.
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01.08.2006; University of Chicago Press; The American Society of Human Genetics
• Subjects: Abnormalities, Multiple - embryology; Abnormalities, Multiple - genetics; Adolescent; Biological and medical sciences; Chromosomes, Human, Pair 2; Diseases of eyelid, conjunctiva and lacrimal tracts; Female; Fetus - abnormalities; General aspects. Genetic counseling; Genetic Variation; Humans; Infant; Male; Medical genetics; Medical sciences; Ophthalmology; Pedigree; Protein Subunits - genetics; Receptors, Cholinergic - genetics; Syndrome; Human; Pterygium; Variant; Eye disease; Cholinergic receptor; Multiple; Genetics; Conjunctiva disease; Mutation; Subunit; Syndrome
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/506256

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 γ 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.