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Clinical and genetic characterization of PYROXD1-related myopathy patients from Turkey       
Yazarlar
Hülya Sevcan Daimagüler
Dr. Öğr. Üyesi Uğur AKPULAT
Kastamonu Üniversitesi, Türkiye
Özkan Özdemir
Türkiye
Uluç Yiş
Türkiye
Serdal Güngör
Türkiye
Beril Talim
Türkiye
Ayşe Gülden Diniz Ünlü
Türkiye
Figen Baydan
Türkiye
Holger Thiele
Janine Altmüller
Peter Nürnberg
Sebahattin Cirak
Özet
Congenital 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.
Anahtar Kelimeler
congenital myopathy | haplotype analysis | LGMD | Mendeliome | PYROXD1 | whole exome sequencing
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı AMERICAN JOURNAL OF MEDICAL GENETICS PART A
Dergi ISSN 1552-4825
Dergi Tarandığı Indeksler SCI-Expanded
Makale Dili Türkçe
Basım Tarihi 06-2021
Cilt No 185
Sayı 6
Sayfalar 1678 / 1690
Doi Numarası 10.1002/ajmg.a.62148
Makale Linki http://dx.doi.org/10.1002/ajmg.a.62148