Recurrent <i>TTN</i> metatranscript‐only c.39974–11T>G splice variant associated with autosomal recessive arthrogryposis multiplex congenita and myopathy
dc.contributor.author | Bryen, Samantha | |
dc.contributor.author | Ewans, LJ | |
dc.contributor.author | Pinner, J | |
dc.contributor.author | MacLennan, SC | |
dc.contributor.author | Donkervoort, S | |
dc.contributor.author | Castro, D | |
dc.contributor.author | Töpf, A | |
dc.contributor.author | O'Grady, G | |
dc.contributor.author | Cummings, B | |
dc.contributor.author | Chao, KR | |
dc.contributor.author | Weisburd, B | |
dc.contributor.author | Francioli, L | |
dc.contributor.author | Faiz, F | |
dc.contributor.author | Bournazos, Adam | |
dc.contributor.author | Hu, Y | |
dc.contributor.author | Grosmann, C | |
dc.contributor.author | Malicki, DM | |
dc.contributor.author | Doyle, H | |
dc.contributor.author | Witting, N | |
dc.contributor.author | Vissing, J | |
dc.contributor.author | Claeys, KG | |
dc.contributor.author | Urankar, K | |
dc.contributor.author | Beleza‐Meireles, A | |
dc.contributor.author | Baptista, Julia | |
dc.contributor.author | Ellard, S | |
dc.contributor.author | Savarese, M | |
dc.contributor.author | Johari, M | |
dc.contributor.author | Vihola, A | |
dc.contributor.author | Udd, B | |
dc.contributor.author | Majumdar, A | |
dc.contributor.author | Straub, V | |
dc.contributor.author | Bönnemann, CG | |
dc.contributor.author | MacArthur, DG | |
dc.contributor.author | Davis, MR | |
dc.contributor.author | Cooper, Sandra | |
dc.date.accessioned | 2022-05-03T18:20:06Z | |
dc.date.issued | 2020-02 | |
dc.identifier.issn | 1059-7794 | |
dc.identifier.issn | 1098-1004 | |
dc.identifier.uri | http://hdl.handle.net/10026.1/19170 | |
dc.description.abstract |
We present eight families with arthrogryposis multiplex congenita and myopathy bearing a TTN intron 213 extended splice-site variant (NM_001267550.1:c.39974-11T>G), inherited in trans with a second pathogenic TTN variant. Muscle-derived RNA studies of three individuals confirmed mis-splicing induced by the c.39974-11T>G variant; in-frame exon 214 skipping or use of a cryptic 3' splice-site effecting a frameshift. Confounding interpretation of pathogenicity is the absence of exons 213-217 within the described skeletal muscle TTN N2A isoform. However, RNA-sequencing from 365 adult human gastrocnemius samples revealed that 56% specimens predominantly include exons 213-217 in TTN transcripts (inclusion rate ≥66%). Further, RNA-sequencing of five fetal muscle samples confirmed that 4/5 specimens predominantly include exons 213-217 (fifth sample inclusion rate 57%). Contractures improved significantly with age for four individuals, which may be linked to decreased expression of pathogenic fetal transcripts. Our study extends emerging evidence supporting a vital developmental role for TTN isoforms containing metatranscript-only exons. | |
dc.format.extent | 403-411 | |
dc.format.medium | Print-Electronic | |
dc.language | en | |
dc.language.iso | eng | |
dc.publisher | Hindawi Limited | |
dc.subject | alternative splicing | |
dc.subject | arthrogryposis | |
dc.subject | congenital titinopathies | |
dc.subject | intronic splice variant | |
dc.subject | TTN metatranscript-only | |
dc.title | Recurrent <i>TTN</i> metatranscript‐only c.39974–11T>G splice variant associated with autosomal recessive arthrogryposis multiplex congenita and myopathy | |
dc.type | journal-article | |
dc.type | Journal Article | |
dc.type | Research Support, N.I.H., Extramural | |
dc.type | Research Support, N.I.H., Intramural | |
dc.type | Research Support, Non-U.S. Gov't | |
plymouth.author-url | https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000500154700001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008 | |
plymouth.issue | 2 | |
plymouth.volume | 41 | |
plymouth.publication-status | Published | |
plymouth.journal | Human Mutation | |
dc.identifier.doi | 10.1002/humu.23938 | |
plymouth.organisational-group | /Plymouth | |
plymouth.organisational-group | /Plymouth/Faculty of Health | |
plymouth.organisational-group | /Plymouth/Faculty of Health/Peninsula Medical School | |
plymouth.organisational-group | /Plymouth/Users by role | |
plymouth.organisational-group | /Plymouth/Users by role/Academics | |
dc.publisher.place | United States | |
dcterms.dateAccepted | 2019-10-24 | |
dc.rights.embargodate | 9999-12-31 | |
dc.identifier.eissn | 1098-1004 | |
dc.rights.embargoperiod | Not known | |
rioxxterms.versionofrecord | 10.1002/humu.23938 | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2020-02 | |
rioxxterms.type | Journal Article/Review |