Mutations in the Cholinergic Receptor Nicotinic Gamma subunit (CHRNG) gene cause autosomal recessive multiple pterygium syndrome.
CHRNG encodes the gamma (γ) subunit of the acetylcholine receptor (AChR) of skeletal muscle. Mutations in genes that encode for AChR subunits are associated with congenital myasthenic syndromes, specifically alterations in α, β, ε, and δ AChR subunits.
The disorder arising from mutations in γ subunit of the nicotinic AChR is peculiar, since γ subunit is expressed in muscle during the prenatal period, contributing to the formation of neuromuscular junctions, but it is not expressed after birth. During development, the γ subunit of AChR is increasingly replaced by the ε subunit, with a switch that occurs around 33 weeks of gestation.
The transient inactivation of the neuromuscular junction during the prenatal period causes prenatal akinesia leading to muscle weakness and severe congenital contractures. Given the fact that CHRNG is expressed only during early fetal development, myasthenic symptoms are absent later in life, but contractures and, in some cases, some permanent weakness may persist.
CHRNG