Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F20%3A10412735" target="_blank" >RIV/00216208:11130/20:10412735 - isvavai.cz</a>
Alternative codes found
RIV/00064203:_____/20:10412735
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=.I8V.26feH" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=.I8V.26feH</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41436-020-0840-3" target="_blank" >10.1038/s41436-020-0840-3</a>
Alternative languages
Result language
angličtina
Original language name
Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness
Original language description
Purpose: Several hundred genetic muscle diseases have been described, all of which are rare. Their clinical and genetic heterogeneity means that a genetic diagnosis is challenging. We established an international consortium, MYO-SEQ, to aid the work-ups of muscle disease patients and to better understand disease etiology. Methods: Exome sequencing was applied to 1001 undiagnosed patients recruited from more than 40 neuromuscular disease referral centers; standardized phenotypic information was collected for each patient. Exomes were examined for variants in 429 genes associated with muscle conditions. Results: We identified suspected pathogenic variants in 52% of patients across 87 genes. We detected 401 novel variants, 116 of which were recurrent. Variants in CAPN3, DYSF, ANO5, DMD, RYR1, TTN, COL6A2, and SGCA collectively accounted for over half of the solved cases; while variants in newer disease genes, such as BVES and POGLUT1, were also found. The remaining well-characterized unsolved patients (48%) need further investigation. Conclusion: Using our unique infrastructure, we developed a pathway to expedite muscle disease diagnoses. Our data suggest that exome sequencing should be used for pathogenic variant detection in patients with suspected genetic muscle diseases, focusing first on the most common disease genes described here, and subsequently in rarer and newly characterized disease genes.
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
30103 - Neurosciences (including psychophysiology)
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Genetics in Medicine
ISSN
1098-3600
e-ISSN
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Volume of the periodical
22
Issue of the periodical within the volume
9
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
1478-1488
UT code for WoS article
000539889800001
EID of the result in the Scopus database
2-s2.0-85086267166