Recurrent TTN metatranscript-only c.39974-11T>G splice variant associated with autosomal recessive arthrogryposis multiplex congenita and myopathy

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Standard

Recurrent TTN metatranscript-only c.39974-11T>G splice variant associated with autosomal recessive arthrogryposis multiplex congenita and myopathy. / Bryen, Samantha J; Ewans, Lisa J; Pinner, Jason; MacLennan, Suzanna C; Donkervoort, Sandra; Castro, Diana; Töpf, Ana; O'Grady, Gina; Cummings, Beryl; Chao, Katherine R; Weisburd, Ben; Francioli, Laurent; Faiz, Fathimath; Bournazos, Adam M; Hu, Ying; Grosmann, Carla; Malicki, Denise M; Doyle, Helen; Witting, Nanna; Vissing, John; Claeys, Kristl G; Urankar, Kathryn; Beleza-Meireles, Ana; Baptista, Julia; Ellard, Sian; Savarese, Marco; Johari, Mridul; Vihola, Anna; Udd, Bjarne; Majumdar, Anirban; Straub, Volker; Bönnemann, Carsten G; MacArthur, Daniel G; Davis, Mark R; Cooper, Sandra T.

In: Human Mutation, Vol. 41, No. 2, 29.10.2020, p. 403-411.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Bryen, SJ, Ewans, LJ, Pinner, J, MacLennan, SC, Donkervoort, S, Castro, D, Töpf, A, O'Grady, G, Cummings, B, Chao, KR, Weisburd, B, Francioli, L, Faiz, F, Bournazos, AM, Hu, Y, Grosmann, C, Malicki, DM, Doyle, H, Witting, N, Vissing, J, Claeys, KG, Urankar, K, Beleza-Meireles, A, Baptista, J, Ellard, S, Savarese, M, Johari, M, Vihola, A, Udd, B, Majumdar, A, Straub, V, Bönnemann, CG, MacArthur, DG, Davis, MR & Cooper, ST 2020, 'Recurrent TTN metatranscript-only c.39974-11T>G splice variant associated with autosomal recessive arthrogryposis multiplex congenita and myopathy', Human Mutation, vol. 41, no. 2, pp. 403-411. https://doi.org/10.1002/humu.23938

APA

Bryen, S. J., Ewans, L. J., Pinner, J., MacLennan, S. C., Donkervoort, S., Castro, D., Töpf, A., O'Grady, G., Cummings, B., Chao, K. R., Weisburd, B., Francioli, L., Faiz, F., Bournazos, A. M., Hu, Y., Grosmann, C., Malicki, D. M., Doyle, H., Witting, N., ... Cooper, S. T. (2020). Recurrent TTN metatranscript-only c.39974-11T>G splice variant associated with autosomal recessive arthrogryposis multiplex congenita and myopathy. Human Mutation, 41(2), 403-411. https://doi.org/10.1002/humu.23938

Vancouver

Bryen SJ, Ewans LJ, Pinner J, MacLennan SC, Donkervoort S, Castro D et al. Recurrent TTN metatranscript-only c.39974-11T>G splice variant associated with autosomal recessive arthrogryposis multiplex congenita and myopathy. Human Mutation. 2020 Oct 29;41(2):403-411. https://doi.org/10.1002/humu.23938

Author

Bryen, Samantha J ; Ewans, Lisa J ; Pinner, Jason ; MacLennan, Suzanna C ; Donkervoort, Sandra ; Castro, Diana ; Töpf, Ana ; O'Grady, Gina ; Cummings, Beryl ; Chao, Katherine R ; Weisburd, Ben ; Francioli, Laurent ; Faiz, Fathimath ; Bournazos, Adam M ; Hu, Ying ; Grosmann, Carla ; Malicki, Denise M ; Doyle, Helen ; Witting, Nanna ; Vissing, John ; Claeys, Kristl G ; Urankar, Kathryn ; Beleza-Meireles, Ana ; Baptista, Julia ; Ellard, Sian ; Savarese, Marco ; Johari, Mridul ; Vihola, Anna ; Udd, Bjarne ; Majumdar, Anirban ; Straub, Volker ; Bönnemann, Carsten G ; MacArthur, Daniel G ; Davis, Mark R ; Cooper, Sandra T. / Recurrent TTN metatranscript-only c.39974-11T>G splice variant associated with autosomal recessive arthrogryposis multiplex congenita and myopathy. In: Human Mutation. 2020 ; Vol. 41, No. 2. pp. 403-411.

Bibtex

@article{49e3e7a1769a410e8ec202e54085ecca,
title = "Recurrent TTN metatranscript-only c.39974-11T>G splice variant associated with autosomal recessive arthrogryposis multiplex congenita and myopathy",
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.",
author = "Bryen, {Samantha J} and Ewans, {Lisa J} and Jason Pinner and MacLennan, {Suzanna C} and Sandra Donkervoort and Diana Castro and Ana T{\"o}pf and Gina O'Grady and Beryl Cummings and Chao, {Katherine R} and Ben Weisburd and Laurent Francioli and Fathimath Faiz and Bournazos, {Adam M} and Ying Hu and Carla Grosmann and Malicki, {Denise M} and Helen Doyle and Nanna Witting and John Vissing and Claeys, {Kristl G} and Kathryn Urankar and Ana Beleza-Meireles and Julia Baptista and Sian Ellard and Marco Savarese and Mridul Johari and Anna Vihola and Bjarne Udd and Anirban Majumdar and Volker Straub and B{\"o}nnemann, {Carsten G} and MacArthur, {Daniel G} and Davis, {Mark R} and Cooper, {Sandra T}",
note = "{\textcopyright} 2019 Wiley Periodicals, Inc.",
year = "2020",
month = oct,
day = "29",
doi = "10.1002/humu.23938",
language = "English",
volume = "41",
pages = "403--411",
journal = "Human Mutation",
issn = "1059-7794",
publisher = "JohnWiley & Sons, Inc.",
number = "2",

}

RIS

TY - JOUR

T1 - Recurrent TTN metatranscript-only c.39974-11T>G splice variant associated with autosomal recessive arthrogryposis multiplex congenita and myopathy

AU - Bryen, Samantha J

AU - Ewans, Lisa J

AU - Pinner, Jason

AU - MacLennan, Suzanna C

AU - Donkervoort, Sandra

AU - Castro, Diana

AU - Töpf, Ana

AU - O'Grady, Gina

AU - Cummings, Beryl

AU - Chao, Katherine R

AU - Weisburd, Ben

AU - Francioli, Laurent

AU - Faiz, Fathimath

AU - Bournazos, Adam M

AU - Hu, Ying

AU - Grosmann, Carla

AU - Malicki, Denise M

AU - Doyle, Helen

AU - Witting, Nanna

AU - Vissing, John

AU - Claeys, Kristl G

AU - Urankar, Kathryn

AU - Beleza-Meireles, Ana

AU - Baptista, Julia

AU - Ellard, Sian

AU - Savarese, Marco

AU - Johari, Mridul

AU - Vihola, Anna

AU - Udd, Bjarne

AU - Majumdar, Anirban

AU - Straub, Volker

AU - Bönnemann, Carsten G

AU - MacArthur, Daniel G

AU - Davis, Mark R

AU - Cooper, Sandra T

N1 - © 2019 Wiley Periodicals, Inc.

PY - 2020/10/29

Y1 - 2020/10/29

N2 - 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.

AB - 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.

U2 - 10.1002/humu.23938

DO - 10.1002/humu.23938

M3 - Journal article

C2 - 31660661

VL - 41

SP - 403

EP - 411

JO - Human Mutation

JF - Human Mutation

SN - 1059-7794

IS - 2

ER -

ID: 236015844