Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness
| العنوان: | Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness |
|---|---|
| المؤلفون: | Ana B. Casasús, Monkol Lek, Elise Valkanas, Eleina M. England, Sabine Specht, Liwen Xu, Jennifer Duff, Thomas Mullen, Magdalena Mroczek, Daniel G. MacArthur, The MYO-SEQ consortium, Volker Straub, Marta Bertoli, Lauren Phillips, Katherine Johnson, Katherine R. Chao, Monica Ensini, Kristen M. Laricchia, Adam Bates, Ana Töpf, Alison Blain |
| المساهمون: | lastentautioppi, Paediatrics and Adolescent Medicine, tyks, vsshp, tyks, vsshp, 2607313 |
| بيانات النشر: | Springer Nature United States Yhdysvallat (USA) US |
| سنة النشر: | 2022 |
| المجموعة: | University of Turku: UTUPub / Turun yliopisto |
| الوصف: | 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. |
| نوع الوثيقة: | other/unknown material |
| اللغة: | English |
| تدمد: | 1530-0366 1098-3600 |
| العلاقة: | 22; Genetics in Medicine; https://www.utupub.fi/handle/10024/159374Test; URN:NBN:fi-fe2021042824405 |
| الإتاحة: | https://www.utupub.fi/handle/10024/159374Test |
| رقم الانضمام: | edsbas.76C12D52 |
| قاعدة البيانات: | BASE |
Full Text Finder | ResultId |
1 |
|---|---|
| Header |
edsbas BASE edsbas.76C12D52 799 3 unknown 799.047973632813 |
| PLink |
https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edsbas&AN=edsbas.76C12D52&custid=s6537998&authtype=sso |
| FullText |
Array
(
[Availability] => 0
)
Array ( [0] => Array ( [Url] => https://www.utupub.fi/handle/10024/159374# [Name] => EDS - BASE [Category] => fullText [Text] => View record in BASE [MouseOverText] => View record in BASE ) [1] => Array ( [Url] => https://resolver.ebscohost.com/openurl?custid=s6537998&groupid=main&authtype=ip,guest&sid=EBSCO:edsbas&genre=article&issn=15300366&ISBN=&volume=&issue=&date=20220101&spage=&pages=&title=Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness&atitle=Sequential%20targeted%20exome%20sequencing%20of%201001%20patients%20affected%20by%20unexplained%20limb-girdle%20weakness&id=DOI: [Name] => Full Text Finder (s6537998api) [Category] => fullText [Text] => Full Text Finder [Icon] => https://imageserver.ebscohost.com/branding/images/FTF.gif [MouseOverText] => Full Text Finder ) ) |
| Items |
Array
(
[Name] => Title
[Label] => Title
[Group] => Ti
[Data] => Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness
)
Array ( [Name] => Author [Label] => Authors [Group] => Au [Data] => <searchLink fieldCode="AR" term="%22Ana+B%2E+Casasús%22">Ana B. Casasús</searchLink><br /><searchLink fieldCode="AR" term="%22Monkol+Lek%22">Monkol Lek</searchLink><br /><searchLink fieldCode="AR" term="%22Elise+Valkanas%22">Elise Valkanas</searchLink><br /><searchLink fieldCode="AR" term="%22Eleina+M%2E+England%22">Eleina M. England</searchLink><br /><searchLink fieldCode="AR" term="%22Sabine+Specht%22">Sabine Specht</searchLink><br /><searchLink fieldCode="AR" term="%22Liwen+Xu%22">Liwen Xu</searchLink><br /><searchLink fieldCode="AR" term="%22Jennifer+Duff%22">Jennifer Duff</searchLink><br /><searchLink fieldCode="AR" term="%22Thomas+Mullen%22">Thomas Mullen</searchLink><br /><searchLink fieldCode="AR" term="%22Magdalena+Mroczek%22">Magdalena Mroczek</searchLink><br /><searchLink fieldCode="AR" term="%22Daniel+G%2E+MacArthur%22">Daniel G. MacArthur</searchLink><br /><searchLink fieldCode="AR" term="%22The+MYO-SEQ+consortium%22">The MYO-SEQ consortium</searchLink><br /><searchLink fieldCode="AR" term="%22Volker+Straub%22">Volker Straub</searchLink><br /><searchLink fieldCode="AR" term="%22Marta+Bertoli%22">Marta Bertoli</searchLink><br /><searchLink fieldCode="AR" term="%22Lauren+Phillips%22">Lauren Phillips</searchLink><br /><searchLink fieldCode="AR" term="%22Katherine+Johnson%22">Katherine Johnson</searchLink><br /><searchLink fieldCode="AR" term="%22Katherine+R%2E+Chao%22">Katherine R. Chao</searchLink><br /><searchLink fieldCode="AR" term="%22Monica+Ensini%22">Monica Ensini</searchLink><br /><searchLink fieldCode="AR" term="%22Kristen+M%2E+Laricchia%22">Kristen M. Laricchia</searchLink><br /><searchLink fieldCode="AR" term="%22Adam+Bates%22">Adam Bates</searchLink><br /><searchLink fieldCode="AR" term="%22Ana+Töpf%22">Ana Töpf</searchLink><br /><searchLink fieldCode="AR" term="%22Alison+Blain%22">Alison Blain</searchLink> ) Array ( [Name] => Author [Label] => Contributors [Group] => Au [Data] => lastentautioppi, Paediatrics and Adolescent Medicine<br />tyks, vsshp, tyks, vsshp<br />2607313 ) Array ( [Name] => Publisher [Label] => Publisher Information [Group] => PubInfo [Data] => Springer Nature<br />United States<br />Yhdysvallat (USA)<br />US ) Array ( [Name] => DatePubCY [Label] => Publication Year [Group] => Date [Data] => 2022 ) Array ( [Name] => Subset [Label] => Collection [Group] => HoldingsInfo [Data] => University of Turku: UTUPub / Turun yliopisto ) Array ( [Name] => Abstract [Label] => Description [Group] => Ab [Data] => 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. ) Array ( [Name] => TypeDocument [Label] => Document Type [Group] => TypDoc [Data] => other/unknown material ) Array ( [Name] => Language [Label] => Language [Group] => Lang [Data] => English ) Array ( [Name] => ISSN [Label] => ISSN [Group] => ISSN [Data] => 1530-0366<br />1098-3600 ) Array ( [Name] => NoteTitleSource [Label] => Relation [Group] => SrcInfo [Data] => 22; Genetics in Medicine; https://www.utupub.fi/handle/10024/159374; URN:NBN:fi-fe2021042824405 ) Array ( [Name] => URL [Label] => Availability [Group] => URL [Data] => https://www.utupub.fi/handle/10024/159374 ) Array ( [Name] => AN [Label] => Accession Number [Group] => ID [Data] => edsbas.76C12D52 ) |
| RecordInfo |
Array
(
[BibEntity] => Array
(
[Languages] => Array
(
[0] => Array
(
[Text] => English
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness
[Type] => main
)
)
)
[BibRelationships] => Array
(
[HasContributorRelationships] => Array
(
[0] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Ana B. Casasús
)
)
)
[1] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Monkol Lek
)
)
)
[2] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Elise Valkanas
)
)
)
[3] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Eleina M. England
)
)
)
[4] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Sabine Specht
)
)
)
[5] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Liwen Xu
)
)
)
[6] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Jennifer Duff
)
)
)
[7] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Thomas Mullen
)
)
)
[8] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Magdalena Mroczek
)
)
)
[9] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Daniel G. MacArthur
)
)
)
[10] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => The MYO-SEQ consortium
)
)
)
[11] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Volker Straub
)
)
)
[12] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Marta Bertoli
)
)
)
[13] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Lauren Phillips
)
)
)
[14] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Katherine Johnson
)
)
)
[15] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Katherine R. Chao
)
)
)
[16] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Monica Ensini
)
)
)
[17] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Kristen M. Laricchia
)
)
)
[18] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Adam Bates
)
)
)
[19] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Ana Töpf
)
)
)
[20] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Alison Blain
)
)
)
[21] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => lastentautioppi, Paediatrics and Adolescent Medicine
)
)
)
[22] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => tyks, vsshp, tyks, vsshp
)
)
)
[23] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => 2607313
)
)
)
)
[IsPartOfRelationships] => Array
(
[0] => Array
(
[BibEntity] => Array
(
[Dates] => Array
(
[0] => Array
(
[D] => 01
[M] => 01
[Type] => published
[Y] => 2022
)
)
[Identifiers] => Array
(
[0] => Array
(
[Type] => issn-print
[Value] => 15300366
)
[1] => Array
(
[Type] => issn-print
[Value] => 10983600
)
[2] => Array
(
[Type] => issn-locals
[Value] => edsbas
)
)
)
)
)
)
)
|
| IllustrationInfo |