multiple pterygium syndrome At least 14 mutations in the CHRNG gene have been found to cause multiple pterygium syndrome, a condition characterized by webbing of the skin (pterygium) and a lack of muscle movement (akinesia) before birth. These mutations include replacing, adding, or deleting DNA building blocks (nucleotides). CHRNG gene mutations result in an impaired or missing γ subunit. The severity of the CHRNG gene mutation influences the severity of the condition. Typically, mutations that prevent the production of any γ subunit will result in lethal multiple pterygium syndrome, which is fatal before birth, while mutations that allow the production of some γ subunit will lead to the milder form of this condition called multiple pterygium syndrome, Escobar type. A shortage of a functional γ subunit prevents the fetal AChR protein from being assembled or properly placed in the muscle cell membrane. As a result, the fetal AChR protein cannot function and the communication between nerve and muscle cells in the developing fetus is impaired. A lack of signaling between nerve and muscle cells leads to akinesia and pterygium before birth, and many of the other signs and symptoms of multiple pterygium syndrome.

     The CHRNG gene provides instructions for making the gamma (γ) protein component (subunit) of the acetylcholine receptor (AChR) protein. The AChR protein is found in the membrane of skeletal muscle cells and is critical for signaling between nerve and muscle cells. Signaling between these cells is necessary for movement. The AChR protein consists of five subunits, each of which is produced from a different gene. The subunits are assembled into the AChR protein in the endoplasmic reticulum, a cell structure involved in protein processing and transport, before being transported to the cell membrane. The γ subunit is found only in the fetal AChR protein. At about the thirty-third week of pregnancy, the γ subunit is replaced by the epsilon (ε) subunit, which is produced by the CHRNE gene, to form the adult AChR protein.

The following transcription factors affect gene expression:

• HNF-1A
• Egr-1
• CREB
• deltaCREB
• HNF-1
• C/EBPalpha
• Roaz
• Msx-1

Molecular Function:

• Acetylcholine-Activated Cation-Selective Channel Activity
• Acetylcholine Receptor Activity
• Channel Activity
• Ligand-Gated Ion Channel Activity

Biological Processes:

• Cation Transmembrane Transport
• Muscle Contraction
• Neuromuscular Synaptic Transmission
• Response To Nicotine
• Signal Transduction
• Synaptic Transmission, Cholinergic
• Transport

Drug Bank:

• Galantamine