{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T23:28:08Z","timestamp":1789687688919,"version":"4.0.1"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T00:00:00Z","timestamp":1701302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Brody Disease is an exceptionally rare, autosomal recessive myopathy attributed to the pathogenic variants in the <jats:italic>ATP2A1<\/jats:italic>, which encodes the sarcoplasmic\/endoplasmic reticulum Ca (2+) ATPase type 1 protein SERCA1. It was first described by Brody IA in 1969. To date, only thirty-three Brody families with forty-seven patients have been reported in the literature, and the disease prevalence is considered as 1 in 10 million, demonstrating the peculiarity of the disease. Clinical characteristics of Brody Disease include muscle stiffness after exercise, myalgia, and muscle cramps. Brody Disease patients generally have disease onset in the first decade, and genetic diagnosis is delayed as a consequence of both the rareness and the mild course of the disease. Here, we report a Turkish Brody Disease patient with a homozygous c.428G&amp;gt;A p.Arg143Gln (NM_004320.4) missense mutation in the <jats:italic>ATP2A1<\/jats:italic>. The male patient, whose symptoms started at the age of 14\u201315, is now 36 years old. His clinical manifestations are athletic appearance, exotropia, slightly elevated creatine kinase (CK), mild progressive proximal muscle weakness in the lower extremities, muscle cramps, pain and stiffness. The patient described here has a very mild progression with an onset in the second\u00a0decade, expanding the Brody Disease phenotype. The study also implies that in the era of emerging genetic therapies, the routine testing of patients with myopathies is a prerequisite since not only future therapies will be designed on molecular findings, but also currently available symptomatic and palliative treatment options will be more precisely applied.<\/jats:p>","DOI":"10.3389\/fgene.2023.1289312","type":"journal-article","created":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T07:56:55Z","timestamp":1701331015000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Case report: Revealing the rare\u2014a Brody Disease patient from Turkey expanding the phenotype"],"prefix":"10.3389","volume":"14","author":[{"given":"Ay\u00e7a","family":"\u015eahin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esmer Zeynep Duru","family":"Badakal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00fcge","family":"Kovanc\u0131lar Ko\u00e7","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilmi","family":"Uysal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ay\u015fe Nazl\u0131","family":"Ba\u015fak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,30]]},"reference":[{"key":"B1","first-page":"37","article-title":"Human Brody disease and its animal model cattle pseudomyotonia: from understanding the pathogenetic mechanism to identification of novel therapeutic approaches","volume-title":"Frontiers in metabolic research","author":"Akyurek","year":"2021"},{"key":"B2","doi-asserted-by":"publisher","first-page":"606254","DOI":"10.3389\/fmolb.2020.606254","article-title":"Deciphering the mechanism of inhibition of SERCA1a by sarcolipin using molecular simulations","volume":"7","author":"Barbot","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1172\/JCI117393","article-title":"Ca2+ homeostasis in Brody\u2019s disease. A study in skeletal muscle and cultured muscle cells and the effects of dantrolene an verapamil","volume":"94","author":"Benders","year":"1994","journal-title":"J. Clin. Investig."},{"key":"B4","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1136\/practneurol-2019-002224","article-title":"Brody disease: when myotonia is not myotonia","volume":"19","author":"Braz","year":"2019","journal-title":"Pract. Neurol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1056\/NEJM196907242810403","article-title":"Muscle contracture induced by exercise. A syndrome attributable to decreased relaxing factor","volume":"281","author":"Brody","year":"1969","journal-title":"N. Engl. J. Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e552","DOI":"10.1002\/mgg3.552","article-title":"Identification of a pathogenic mutation in ATP2A1 via in silico analysis of exome data for cryptic aberrant splice sites","volume":"7","author":"Bruels","year":"2019","journal-title":"Mol. Genet. Genomic Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1016\/j.nmd.2020.12.003","article-title":"Next-generation sequencing application to investigate skeletal muscle channelopathies in a large cohort of Italian patients","volume":"31","author":"Brugnoni","year":"2021","journal-title":"Neuromuscul. Disord."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.4172\/2157-7412.1000181","article-title":"Fourty-four years of Brody disease: it is time to Review","volume":"4","author":"Guglielmi","year":"2013","journal-title":"J. Genet. Syndr. Gene Ther."},{"key":"B9","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1002\/ana.410200108","article-title":"Myopathy caused by a deficiency of Ca2+-adenosine triphosphatase in sarcoplasmic reticulum (Brody\u2019s disease)","volume":"20","author":"Karpati","year":"1986","journal-title":"Ann. Neurol."},{"key":"B10","volume-title":"Berne and levy physiology e-book","author":"Koeppen","year":"2023"},{"key":"B11","first-page":"A9675","article-title":"Overactive muscles: it can be more serious than common myalgia or cramp","volume":"160","author":"Molenaar","year":"2016","journal-title":"Ned. Tijdschr. Geneeskd."},{"key":"B12","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1093\/brain\/awz410","article-title":"Clinical, morphological and genetic characterization of Brody disease: an international study of 40 patients","volume":"143","author":"Molenaar","year":"2020","journal-title":"Brain"},{"key":"B13","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1007\/s004390000297","article-title":"The mutation of Pro789 to Leu reduces the activity of the fast-twitch skeletal muscle sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA1) and is associated with Brody disease","volume":"106","author":"Odermatt","year":"2000","journal-title":"Hum. Genet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1038\/ng1096-191","article-title":"Mutations in the gene\u2013encoding SERCA1, the fast\u2013twitch skeletal muscle sarcoplasmic reticulum Ca2+ ATPase, are associated with Brody disease","volume":"14","author":"Odermatt","year":"1996","journal-title":"Nat. Genet."},{"key":"B15","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1111\/ahg.12429","article-title":"Mutation spectrum of hereditary myopathies in Turkish patients and novel variants","volume":"85","author":"Saat","year":"2021","journal-title":"Ann. Hum. Genet."},{"key":"B16","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1002\/mgg3.91","article-title":"Exome analysis identifies Brody myopathy in a family diagnosed with malignant hyperthermia susceptibility","volume":"2","author":"Sambuughin","year":"2014","journal-title":"Mol. Genet. Genomic Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"93","DOI":"10.18229\/kocatepetip.656268","article-title":"CALCIUM ADENOSINE 5\u2019 TRIPHOSPHATASE ENZYME ACTIVITY IN EXTRAOCULAR MUSCLES IN STRABISMUS","volume":"22","author":"To\u011frul","year":"2021","journal-title":"KTD"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1170071","DOI":"10.3389\/fneur.2023.1170071","article-title":"Case report: clinical and molecular characterization of two siblings affected by Brody myopathy","volume":"14","author":"Velardo","year":"2023","journal-title":"Front. Neurol."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000202716","article-title":"Brody myopathy associated with novel compound heterozygous ATP2A1 mutations (P6-8.015)","volume":"100","author":"Walia","year":"2023","journal-title":"Neurology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/S0143416002001847","article-title":"Molecular physiology of the SERCA and SPCA pumps","volume":"32","author":"Wuytack","year":"2002","journal-title":"Cell. Calcium"},{"key":"B21","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s13395-021-00280-7","article-title":"The SarcoEndoplasmic Reticulum Calcium ATPase (SERCA) pump: a potential target for intervention in aging and skeletal muscle pathologies","volume":"11","author":"Xu","year":"2021","journal-title":"Skelet. Muscle"}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2023.1289312\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T10:21:35Z","timestamp":1701858095000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2023.1289312\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,30]]},"references-count":21,"alternative-id":["10.3389\/fgene.2023.1289312"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2023.1289312","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,30]]},"article-number":"1289312"}}