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: Neil V Morgan, Louise A Brueton, Phillip Cox, Marie T Greally, John Tolmie, Shanaz Pasha, Irene A Aligianis, Hans van Bokhoven, Tamas Marton, Lihadh Al-Gazali, Jenny E V Morton, Christine Oley, Colin A Johnson, Richard C Trembath, Han G Brunner, Eamonn R Maher
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 79 Issue 2 Pg. 390-5 (Aug 2006) ISSN: 0002-9297 [Print] United States
• PMID: 16826531 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Protein Subunits
• Receptors, Cholinergic

Topics

• Abnormalities, Multiple (embryology, genetics)
• Adolescent
• Chromosomes, Human, Pair 2
• Female
• Fetus (abnormalities)
• Genetic Variation
• Humans
• Infant
• Male
• Pedigree
• Protein Subunits (genetics)
• Receptors, Cholinergic (genetics)
• Syndrome