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| Item Type: | Article |
|---|---|
| Title: | Clinical and genetic characterization of PYROXD1-related myopathy patients from Turkey |
| Creators Name: | Daimagüler, H.S., Akpulat, U., Özdemir, Ö., Yis, U., Güngör, S., Talim, B., Diniz, G., Baydan, F., Thiele, H., Altmüller, J., Nürnberg, P. and Cirak, S. |
| Abstract: | 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. |
| Keywords: | Congenital Myopathy, Haplotype Analysis, LGMD, Mendeliome, PYROXD1, Whole Exome Sequencing |
| Source: | American Journal of Medical Genetics A |
| ISSN: | 1552-4825 |
| Publisher: | Wiley |
| Volume: | 185 |
| Number: | 6 |
| Page Range: | 1678-1690 |
| Date: | 14 May 2021 |
| Official Publication: | https://doi.org/10.1002/ajmg.a.62148 |
| PubMed: | View item in PubMed |
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