| 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 |
| Atıf Sayıları | |
| WoS | 4 |
| SCOPUS | 6 |
| Google Scholar | 9 |
