| Autor: |
Mroczek, Magdalena, Inashkina, Inna, Stavusis, Janis, Zayakin, Pawel, Khrunin, Andrey, Micule, Ieva, Kenina, Victorija, Zdanovica, Anna, Zídková, Jana, Fajkusová, Lenka, Limborska, Svetlana, van der Kooi, Anneke J., Brusse, Esther, Leonardis, Lea, Maver, Ales, Pajusalu, Sander, Õunap, Katrin, Puusepp, Sanna, Dobosz, Paula, Sypniewski, Mateusz |
| Zdroj: |
Human Mutation; Oct2022, Vol. 43 Issue 10, p1347-1353, 7p |
| Abstrakt: |
The investigated intronic CAPN3 variant NM_000070.3:c.1746‐20C>G occurs in the Central and Eastern Europe with a frequency of >1% and there are conflicting interpretations on its pathogenicity. We collected data on 14 patients carrying the CAPN3 c.1746‐20C>G variant in trans position with another CAPN3 pathogenic/likely pathogenic variant. The patients compound heterozygous for the CAPN3 c.1746‐20C>G variant presented a phenotype consistent with calpainopathy of mild/medium severity. This variant is most frequent in the North/West regions of Russia and may originate from that area. Molecular studies revealed that different splicing isoforms are produced in the muscle. We hypothesize that c.1746‐20C>G is a hypomorphic variant with a reduction of RNA and protein expression and only individuals having a higher ratio of abnormal isoforms are affected. Reclassification of the CAPN3 variant c.1746‐20C>G from variant with a conflicting interpretation of pathogenicity to hypomorphic variant explains many unidentified cases of limb girdle muscular dystrophy R1 calpain 3‐related in Eastern and Central Europe. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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