{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The delta subunit of the muscle nicotinic acetylcholine receptor—encoded by the"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "and discussed in multiple studies—plays a critical role in the assembly, gating, and overall function of the receptor at the neuromuscular junction. It is a key structural component necessary for proper synaptic transmission in skeletal muscle, and alterations in its structure or expression can disrupt neuromuscular signaling. Mutations or genetic variations that affect "}, {"type": "b", "children": [{"type": "t", "text": "CHRND"}]}, {"type": "t", "text": " have been implicated in a variety of neuromuscular disorders. For example, severe loss‐of‐function mutations may contribute to lethal phenotypes such as fetal akinesia deformation sequence and multiple pterygium syndromes, where impaired acetylcholine receptor formation leads to markedly reduced neuromuscular transmission."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In contrast, heterozygous or milder alterations in "}, {"type": "b", "children": [{"type": "t", "text": "CHRND"}]}, {"type": "t", "text": " can underlie congenital myasthenic syndromes, including slow-channel variants that are characterized by prolonged channel opening and consequent muscle fatigability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Genetic association studies have also noted that specific alleles within the receptor gene clusters—including those containing "}, {"type": "b", "children": [{"type": "t", "text": "CHRND"}]}, {"type": "t", "text": "—may modify susceptibility to conditions such as nicotine dependence and autoimmune myasthenia gravis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", even though not all investigations consistently implicate "}, {"type": "b", "children": [{"type": "t", "text": "CHRND"}]}, {"type": "t", "text": " in every neuromuscular or developmental disorder."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, cross‐species mapping studies reinforce the evolutionary conservation of the "}, {"type": "b", "children": [{"type": "t", "text": "CHRND"}]}, {"type": "t", "text": " locus, supporting its fundamental role in neuromuscular function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, the delta subunit is indispensable for the normal development and transmission at the neuromuscular junction. Its disruption—through mutations that alter receptor assembly, kinetics, or expression—can lead to a spectrum of clinical manifestations ranging from congenital myasthenic syndromes with variable severity to developmental disorders characterized by fetal akinesia. At the same time, common variations in this gene may contribute to differences in disease susceptibility in broader contexts.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nancy L Saccone, Scott F Saccone, Anthony L Hinrichs, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Multiple distinct risk loci for nicotine dependence identified by dense coverage of the complete family of nicotinic receptor subunit (CHRN) genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet B Neuropsychiatr Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.b.30828"}], "href": "https://doi.org/10.1002/ajmg.b.30828"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19259974"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19259974"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Anne Michalk, Sigmar Stricker, Jutta Becker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Acetylcholine receptor pathway mutations explain various fetal akinesia deformation sequence disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2007.11.006"}], "href": "https://doi.org/10.1016/j.ajhg.2007.11.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18252226"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18252226"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "J Vogt, N V Morgan, T Marton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Germline mutation in DOK7 associated with fetal akinesia deformation sequence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.2008.065425"}], "href": "https://doi.org/10.1136/jmg.2008.065425"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19261599"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19261599"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yong Liu, Shuxin Ye, Haiyan Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Clinical and genetic analysis of a patient with slow-channel congenital myasthenic syndrome]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Zhonghua Yi Xue Yi Chuan Xue Za Zhi (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3760/cma.j.issn.1003-9406.2020.05.014"}], "href": "https://doi.org/10.3760/cma.j.issn.1003-9406.2020.05.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32335884"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32335884"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "N L Saccone, T-H Schwantes-An, J C Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Multiple cholinergic nicotinic receptor genes affect nicotine dependence risk in African and European Americans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Brain Behav (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1601-183X.2010.00608.x"}], "href": "https://doi.org/10.1111/j.1601-183X.2010.00608.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20584212"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20584212"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "M Giraud, B Eymard, C Tranchant, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of the gene encoding the delta-subunit of the muscle acetylcholine receptor (CHRND) with acquired autoimmune myasthenia gravis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Immun (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.gene.6364041"}], "href": "https://doi.org/10.1038/sj.gene.6364041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14735155"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14735155"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Julie Vogt, Benjamin J Harrison, Hayley Spearman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation analysis of CHRNA1, CHRNB1, CHRND, and RAPSN genes in multiple pterygium syndrome/fetal akinesia patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2007.09.016"}], "href": "https://doi.org/10.1016/j.ajhg.2007.09.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18179903"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18179903"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "P R Jarman, M B Davis, S V Hodgson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Paroxysmal dystonic choreoathetosis. Genetic linkage studies in a British family."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain (1997)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/brain/120.12.2125"}], "href": "https://doi.org/10.1093/brain/120.12.2125"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "9448567"}], "href": "https://pubmed.ncbi.nlm.nih.gov/9448567"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "H A Ansari, P D Pearce, D W Maher, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regional mapping of loci from human chromosome 2q to sheep chromosome 2q."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genomics (1994)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1006/geno.1994.1137"}], "href": "https://doi.org/10.1006/geno.1994.1137"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "8020939"}], "href": "https://pubmed.ncbi.nlm.nih.gov/8020939"}]}]}]}