CAPN3 c.1746-20C>G variant is hypomorphic for LGMD R1 calpain 3-related
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F22%3A00076609" target="_blank" >RIV/65269705:_____/22:00076609 - isvavai.cz</a>
Result on the web
<a href="https://onlinelibrary.wiley.com/doi/10.1002/humu.24421" target="_blank" >https://onlinelibrary.wiley.com/doi/10.1002/humu.24421</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/humu.24421" target="_blank" >10.1002/humu.24421</a>
Alternative languages
Result language
angličtina
Original language name
CAPN3 c.1746-20C>G variant is hypomorphic for LGMD R1 calpain 3-related
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10603 - Genetics and heredity (medical genetics to be 3)
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Human Mutation
ISSN
1059-7794
e-ISSN
1098-1004
Volume of the periodical
43
Issue of the periodical within the volume
10
Country of publishing house
US - UNITED STATES
Number of pages
7
Pages from-to
1347-1353
UT code for WoS article
000814217900001
EID of the result in the Scopus database
2-s2.0-85132317495