CHRNG, which encodes the γ subunit of the embryonal acetylcholine receptor, is crucial for normal neuromuscular junction function. The nicotinic acetylcholine receptor is a transmembrane protein essential for neuromuscular signal transmission, and CHRNG-related processes are integral to muscle development and function [2,3,4].

Mutations in CHRNG cause autosomal recessive multiple pterygium syndrome (MPS), including the non-lethal Escobar variant (EVMPS) and the lethal form (LMPS). Patients with CHRNG-related non-lethal MPS show a phenotype of multiple congenital contractures, pterygium, and facial dysmorphism, along with postnatal neuromuscular junction abnormalities. Whole-body magnetic resonance imaging reveals marked muscle bulk reduction, especially in spinal erector and gluteus maximus muscles, and fatty infiltration in deep paravertebral and distal lower limb muscles [1]. CHRNG mutations are mainly located at the extracellular domain of the protein [1]. In different families with the same CHRNG mutation, both EVMPS and LMPS phenotypes can be observed, indicating intrafamilial variability [3]. Also, overexpression of CHRNG in bovine preadipocytes inhibits their proliferation and differentiation [5].

In summary, CHRNG is vital for normal neuromuscular junction function and muscle-related processes. Studies of CHRNG-associated mutations in MPS cases have deepened our understanding of the gene's role in muscle development and disease. These findings may assist in differentiating MPS from other diffuse arthrogryposis entities and contribute to a better understanding of the molecular mechanisms underlying muscle-related disorders [1,3].

References:

1. Carrera-García, Laura, Natera-de Benito, Daniel, Dieterich, Klaus, Quijano-Roy, Susana, Nascimento, Andres. 2019. CHRNG-related nonlethal multiple pterygium syndrome: Muscle imaging pattern and clinical, histopathological, and molecular genetic findings. In American journal of medical genetics. Part A, 179, 915-926. doi:10.1002/ajmg.a.61122. https://pubmed.ncbi.nlm.nih.gov/30868735/

2. Ohno, Kinji, Ohkawara, Bisei, Shen, Xin-Ming, Selcen, Duygu, Engel, Andrew G. 2023. Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review. In International journal of molecular sciences, 24, . doi:10.3390/ijms24043730. https://pubmed.ncbi.nlm.nih.gov/36835142/

3. Vogt, Julie, Morgan, Neil V, Rehal, Pauline, MacDonald, Fiona, Maher, Eamonn R. . CHRNG genotype-phenotype correlations in the multiple pterygium syndromes. In Journal of medical genetics, 49, 21-6. doi:10.1136/jmedgenet-2011-100378. https://pubmed.ncbi.nlm.nih.gov/22167768/

4. Kariminejad, Ariana, Almadani, Navid, Khoshaeen, Atefeh, Moslemi, Ali-Reza, Tajsharghi, Homa. 2016. Truncating CHRNG mutations associated with interfamilial variability of the severity of the Escobar variant of multiple pterygium syndrome. In BMC genetics, 17, 71. doi:10.1186/s12863-016-0382-5. https://pubmed.ncbi.nlm.nih.gov/27245440/

5. Du, Jiawei, Zhao, Hui, Song, Guibing, Zan, Linsen, Wang, Hongbao. 2022. Overexpression of cholinergic receptor nicotinic gamma subunit inhibits proliferation and differentiation of bovine preadipocytes. In Animal bioscience, 36, 200-208. doi:10.5713/ab.22.0144. https://pubmed.ncbi.nlm.nih.gov/36108684/