{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T12:59:51Z","timestamp":1775912391650,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T00:00:00Z","timestamp":1615334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Congenital myopathies (CMs) are a heterogeneous group of inherited muscle disorders characterized by muscle weakness at birth, while limb\u2010girdle muscular dystrophies (LGMD) have a later onset and slower disease progression. Thus, detailed clinical phenotyping of genetically defined disease entities are required for the full understanding of genotype\u2013phenotype correlations. A recently defined myopathic genetic disease entity is caused by bi\u2010allelic variants in a gene coding for pyridine nucleotide\u2010disulfide oxidoreductase domain 1 (<jats:italic>PYROXD1<\/jats:italic>) with unknown substrates. Here, we present three patients from two consanguineous Turkish families with mild LGMD, facial weakness, normal CK levels, and slow progress. Genomic analyses revealed a homozygous known pathogenic missense variant (c.464A&gt;G, p.Asn155Ser) in family 1 with two affected females. In the affected male of family 2, we found this variant in a compound heterozygous state together with a novel frameshift variant (c.329_332delTCTG, p.Leu112Valfs*8), which is the second frameshift variant known so far in <jats:italic>PYROXD1<\/jats:italic>. We have been able to define a large homozygous region in family 1 sharing a common haplotype with family 2 in the critical region. Our data suggest that c.464A&gt;G is a Turkish founder mutation. To gain deeper insights, we performed a systematic review of all published <jats:italic>PYROXD1<\/jats:italic>\u2010related myopathy cases. Our analysis showed that the c.464A\u2009&gt;\u2009G variant was found in 87% (20\/23) of the patients and that it may cause either a childhood\u2010 or adult\u2010onset phenotype, irrespective of its presence in a homozygous or compound heterozygous state. Interestingly, only four patients had elevated CK levels (up to 1000\u2009U\/L), and cardiac involvement was found in few compound heterozygous cases.<\/jats:p>","DOI":"10.1002\/ajmg.a.62148","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T05:50:06Z","timestamp":1615441806000},"page":"1678-1690","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Clinical and genetic characterization of <scp><i>PYROXD1<\/i><\/scp>\u2010related myopathy patients from Turkey"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8874-8125","authenticated-orcid":false,"given":"H\u00fclya\u2010Sevcan","family":"Daimag\u00fcler","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Cologne, Faculty of Medicine and University Hospital Cologne  Cologne Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), University of Cologne Faculty of Medicine and University Hospital Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ugur","family":"Akpulat","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Cologne, Faculty of Medicine and University Hospital Cologne  Cologne Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), University of Cologne Faculty of Medicine and University Hospital Cologne  Cologne Germany"},{"name":"Department of Medical Biology, Faculty of Medicine Kastamonu University  Kastamonu Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2647-6416","authenticated-orcid":false,"given":"\u00d6zkan","family":"\u00d6zdemir","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Cologne, Faculty of Medicine and University Hospital Cologne  Cologne Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), University of Cologne Faculty of Medicine and University Hospital Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uluc","family":"Yis","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Pediatric Neurology Izmir Dokuz Eyl\u00fcl University  Izmir Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serdal","family":"G\u00fcng\u00f6r","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Turgut Ozal Research Center, Department of Paediatric Neurology In\u00f6n\u00fc University Malatya  Malatya Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beril","family":"Talim","sequence":"additional","affiliation":[{"name":"Pediatric Pathology Unit, Department of Pediatrics Hacettepe University Ankara  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00fclden","family":"Diniz","sequence":"additional","affiliation":[{"name":"Department of Pathology Izmir Democracy University  Izmir Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Figen","family":"Baydan","sequence":"additional","affiliation":[{"name":"Division of Child Neurology Tepecik Training and Research Hospital  \u0130zmir Turkey"},{"name":"Neuromuscular Disease Center Tepecik Training and Research Hospital  \u0130zmir Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holger","family":"Thiele","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics (CCG) University of Cologne and University Hospital Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janine","family":"Altm\u00fcller","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics (CCG) University of Cologne and University Hospital Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"N\u00fcrnberg","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Cologne (CMMC), University of Cologne Faculty of Medicine and University Hospital Cologne  Cologne Germany"},{"name":"Cologne Center for Genomics (CCG) University of Cologne and University Hospital Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebahattin","family":"Cirak","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Cologne, Faculty of Medicine and University Hospital Cologne  Cologne Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), University of Cologne Faculty of Medicine and University Hospital Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,3,10]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21644"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.2890"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103074200"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.14365"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-019-0869-1"},{"key":"e_1_2_11_7_1","volume-title":"Muscle biopsy: A practical approach","author":"Dubowitz 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