Chrnb1, encoding the β subunit of the acetylcholine receptor (AChR) at the neuromuscular junction, is crucial for normal neuromuscular signal transmission. The AChR is integral to the process of muscle contraction as it mediates the communication between motor neurons and muscle fibers. Dysfunctions in this gene can disrupt this key physiological pathway [1,2,3].

Inherited defects in Chrnb1 can lead to congenital myasthenia syndrome (CMS), a clinically and genetically heterogeneous disorder. In severe cases, it can result in fetal akinesia deformation sequence (FADS). Two unrelated families with biallelic Chrnb1 variants were reported, where in each family, one child presented with lethal FADS [1]. Also, a frameshift mutation in Chrnb1 was associated with familial arthrogryposis multiplex congenita in Red dairy cattle, suggesting a similar underlying neuromuscular disorder as in human CMS [3].

In conclusion, Chrnb1 is essential for proper neuromuscular function. Research on Chrnb1, especially through cases of genetic mutations in humans and animals, has revealed its significance in CMS and related severe phenotypes like FADS and bovine arthrogryposis multiplex congenita. Understanding Chrnb1 can potentially lead to better diagnostic and treatment strategies for these neuromuscular disorders.

References:

1. Freed, Amanda S, Schwarz, Anisha C, Brei, Brianna K, Innes, A Micheil, Bennett, James T. 2020. CHRNB1-associated congenital myasthenia syndrome: Expanding the clinical spectrum. In American journal of medical genetics. Part A, 185, 827-835. doi:10.1002/ajmg.a.62011. https://pubmed.ncbi.nlm.nih.gov/33296147/

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. Agerholm, Jørgen S, McEvoy, Fintan J, Menzi, Fiona, Jagannathan, Vidhya, Drögemüller, Cord. 2016. A CHRNB1 frameshift mutation is associated with familial arthrogryposis multiplex congenita in Red dairy cattle. In BMC genomics, 17, 479. doi:10.1186/s12864-016-2832-x. https://pubmed.ncbi.nlm.nih.gov/27364156/