{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nDelta‐sarcoglycan (SGCD) is a critical structural protein that functions as an integral component of the sarcoglycan complex, which itself is part of the larger dystrophin–glycoprotein complex. In skeletal muscle, immunoanalysis has revealed that reduced or absent expression of one or several sarcoglycans—including δ‐sarcoglycan—contributes to limb‐girdle muscular dystrophy. Moreover, experimental evidence shows that β‐ and δ‐sarcoglycan interact to form a core subcomplex that is essential for efficient export from the endoplasmic reticulum and proper deposition at the plasma membrane, thereby ensuring sarcolemmal integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn cardiac muscle, SGCD plays a pivotal role in preserving plasma membrane stability during mechanical stress. In a mouse model, loss of δ‐sarco­glycan function was shown to promote hypertrophic cardiomyopathy and coronary spasm, underscoring its importance in maintaining normal cardiac contractility. In human studies, promoter polymorphisms and missense mutations in SGCD have been demonstrated to decrease promoter activity and disrupt plasma membrane localization of the sarcoglycan subcomplex; such alterations contribute to increased susceptibility to dilated cardiomyopathy. Furthermore, familial analyses indicate that while homozygous loss‐of-function mutations in SGCD can lead to limb–girdle muscular dystrophy, the co-occurrence of specific SGCD variants in compound heterozygotes may mitigate the development of cardiomyopathy, thereby questioning the pathogenicity of some mutations previously thought to act in a dominant manner."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSGCD gene alterations have also been implicated in extra‐muscular and developmental contexts. A non‐synonymous mutation in SGCD has been identified among patients with total anomalous pulmonary venous return, suggesting a role in developmental cardiac anomalies. In addition, specific single nucleotide polymorphisms in the SGCD gene are associated with obstructive sleep apnea, perhaps through effects on airway muscle function and pharyngeal stability. Finally, studies in the Syrian cardiomyopathic hamster model—characterized by a deletion at the SGCD locus—demonstrate disturbed catecholamine metabolism, implying that SGCD function may extend to regulating exocytotic pathways and neuroendocrine homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lars Klinge, Gabriele Dekomien, Ahmed Aboumousa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sarcoglycanopathies: can muscle immunoanalysis predict the genotype?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuromuscul Disord (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.nmd.2008.08.003"}], "href": "https://doi.org/10.1016/j.nmd.2008.08.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18996010"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18996010"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Romesh A Draviam, Stuart H Shand, Simon C Watkins "}, {"type": "b", "children": [{"type": "t", "text": "The beta-delta-core of sarcoglycan is essential for deposition at the plasma membrane."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Muscle Nerve (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mus.20640"}], "href": "https://doi.org/10.1002/mus.20640"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17036316"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17036316"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tsuyoshi Honda, Seigo Sugiyama, Tomohiro Sakamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impact of delta-sarcoglycan gene polymorphism on the occurrence of coronary spastic angina in Japanese patients with hypertrophic cardiomyopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ J (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1253/circj.71.1263"}], "href": "https://doi.org/10.1253/circj.71.1263"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17652892"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17652892"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jie Chen, Ye Jin, Hong Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Haplotype of Two Novel Polymorphisms in δ-Sarcoglycan Gene Increases Risk of Dilated Cardiomyopathy in Mongoloid Population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0145602"}], "href": "https://doi.org/10.1371/journal.pone.0145602"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26720722"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26720722"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Matthew D Campbell, Marc Witcher, Anoop Gopal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dilated cardiomyopathy mutations in δ-sarcoglycan exert a dominant-negative effect on cardiac myocyte mechanical stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Heart Circ Physiol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpheart.00521.2015"}], "href": "https://doi.org/10.1152/ajpheart.00521.2015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26968544"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26968544"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ralf Bauer, Judith Hudson, Harald D Müller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Does delta-sarcoglycan-associated autosomal-dominant cardiomyopathy exist?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejhg.2009.17"}], "href": "https://doi.org/10.1038/ejhg.2009.17"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19259135"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19259135"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jun Li, Shiwei Yang, Zhening Pu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Whole-exome sequencing identifies SGCD and ACVRL1 mutations associated with total anomalous pulmonary venous return (TAPVR) in Chinese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.15434"}], "href": "https://doi.org/10.18632/oncotarget.15434"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28412737"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28412737"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Rensong Ye, Wenlan Yang, Yiming Yuan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The CC genotype of the delta-sarcoglycan gene polymorphism rs13170573 is associated with obstructive sleep apnea in the Chinese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0114160"}], "href": "https://doi.org/10.1371/journal.pone.0114160"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25474115"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25474115"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "C Makena Hightower, Kuixing Zhang, José P Miramontes-González, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variation at the delta-sarcoglycan (SGCD) locus elevates heritable sympathetic nerve activity in human twin pairs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurochem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jnc.12346"}], "href": "https://doi.org/10.1111/jnc.12346"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23786442"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23786442"}]}]}]}