Clinical and genetic characterization of PYROXD1-related myopathy patients from Turkey

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dc.authoridozdemir, ozkan/0000-0002-2647-6416
dc.authoridDiniz, Gulden/0000-0003-1512-7584
dc.authoridDaimaguler, Hulya-Sevcan/0000-0001-8874-8125
dc.authoridAltmuller, Janine/0000-0003-4372-1521
dc.authorwosidAkpulat, Ugur/JHU-1854-2023
dc.authorwosidozdemir, ozkan/AAI-9947-2021
dc.authorwosidCirak, Sebahattin/AAX-9593-2020
dc.authorwosidTALIM, BERIL/I-9103-2013
dc.authorwosidDiniz, Gulden/HKM-3640-2023
dc.contributor.authorDaimagueler, Huelya-Sevcan
dc.contributor.authorAkpulat, Ugur
dc.contributor.authorOezdemir, Oezkan
dc.contributor.authorYis, Uluc
dc.contributor.authorGungor, Serdal
dc.contributor.authorTalim, Beril
dc.contributor.authorDiniz, Gulden
dc.date.accessioned2024-08-04T20:49:23Z
dc.date.available2024-08-04T20:49:23Z
dc.date.issued2021
dc.departmentİnönü Üniversitesien_US
dc.description.abstractCongenital myopathies (CMs) are a heterogeneous group of inherited muscle disorders characterized by muscle weakness at birth, while limb-girdle 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-phenotype correlations. A recently defined myopathic genetic disease entity is caused by bi-allelic variants in a gene coding for pyridine nucleotide-disulfide oxidoreductase domain 1 (PYROXD1) 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>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 PYROXD1. 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>G is a Turkish founder mutation. To gain deeper insights, we performed a systematic review of all published PYROXD1-related myopathy cases. Our analysis showed that the c.464A > G variant was found in 87% (20/23) of the patients and that it may cause either a childhood- or adult-onset phenotype, irrespective of its presence in a homozygous or compound heterozygous state. Interestingly, only four patients had elevated CK levels (up to 1000 U/L), and cardiac involvement was found in few compound heterozygous cases.en_US
dc.description.sponsorshipDeutsche Forschungsgemeinschaft, Germany grants [Cl 218/1-1]; Koln Fortune Grants; Projekt DEALen_US
dc.description.sponsorshipWe thank the patients and their families contributing to this clinical study. This work was supported by the Deutsche Forschungsgemeinschaft, Germany grants (Cl 218/1-1) and Koln Fortune Grants to SC. Open access funding enabled and organized by Projekt DEAL.en_US
dc.identifier.doi10.1002/ajmg.a.62148
dc.identifier.endpage1690en_US
dc.identifier.issn1552-4825
dc.identifier.issn1552-4833
dc.identifier.issue6en_US
dc.identifier.pmid33694278en_US
dc.identifier.scopus2-s2.0-85102266424en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage1678en_US
dc.identifier.urihttps://doi.org/10.1002/ajmg.a.62148
dc.identifier.urihttps://hdl.handle.net/11616/99808
dc.identifier.volume185en_US
dc.identifier.wosWOS:000627172300001en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofAmerican Journal of Medical Genetics Part Aen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectcongenital myopathyen_US
dc.subjecthaplotype analysisen_US
dc.subjectLGMDen_US
dc.subjectMendeliomeen_US
dc.subjectPYROXD1en_US
dc.subjectwhole exome sequencingen_US
dc.titleClinical and genetic characterization of PYROXD1-related myopathy patients from Turkeyen_US
dc.typeArticleen_US

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