Research ExplorerPublicationsPOPDC1(S201F) causes muscular dystrophy and arrhythmia by af...

POPDC1(S201F) causes muscular dystrophy and arrhythmia by affecting protein trafficking

Standard

POPDC1(S201F) causes muscular dystrophy and arrhythmia by affecting protein trafficking. / Schindler, Roland F R; Scotton, Chiara; Zhang, Jianguo; Passarelli, Chiara; Ortiz-Bonnin, Beatriz; Simrick, Subreena; Schwerte, Thorsten; Poon, Kar-Lai; Fang, Mingyan; Rinné, Susanne; Froese, Alexander; Nikolaev, Viacheslav O; Grunert, Christiane; Müller, Thomas; Tasca, Giorgio; Sarathchandra, Padmini; Drago, Fabrizio; Dallapiccola, Bruno; Rapezzi, Claudio; Arbustini, Eloisa; Di Raimo, Francesca Romana; Neri, Marcella; Selvatici, Rita; Gualandi, Francesca; Fattori, Fabiana; Pietrangelo, Antonello; Li, Wenyan; Jiang, Hui; Xu, Xun; Bertini, Enrico; Decher, Niels; Wang, Jun; Brand, Thomas; Ferlini, Alessandra.

In: J CLIN INVEST, Vol. 126, No. 1, 01.2016, p. 239-53.

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

Harvard

Schindler, RFR, Scotton, C, Zhang, J, Passarelli, C, Ortiz-Bonnin, B, Simrick, S, Schwerte, T, Poon, K-L, Fang, M, Rinné, S, Froese, A, Nikolaev, VO, Grunert, C, Müller, T, Tasca, G, Sarathchandra, P, Drago, F, Dallapiccola, B, Rapezzi, C, Arbustini, E, Di Raimo, FR, Neri, M, Selvatici, R, Gualandi, F, Fattori, F, Pietrangelo, A, Li, W, Jiang, H, Xu, X, Bertini, E, Decher, N, Wang, J, Brand, T & Ferlini, A 2016, 'POPDC1(S201F) causes muscular dystrophy and arrhythmia by affecting protein trafficking', J CLIN INVEST, vol. 126, no. 1, pp. 239-53. https://doi.org/10.1172/JCI79562

APA

Schindler, R. F. R., Scotton, C., Zhang, J., Passarelli, C., Ortiz-Bonnin, B., Simrick, S., Schwerte, T., Poon, K-L., Fang, M., Rinné, S., Froese, A., Nikolaev, V. O., Grunert, C., Müller, T., Tasca, G., Sarathchandra, P., Drago, F., Dallapiccola, B., Rapezzi, C., ... Ferlini, A. (2016). POPDC1(S201F) causes muscular dystrophy and arrhythmia by affecting protein trafficking. J CLIN INVEST, 126(1), 239-53. https://doi.org/10.1172/JCI79562

Vancouver

Schindler RFR, Scotton C, Zhang J, Passarelli C, Ortiz-Bonnin B, Simrick S et al. POPDC1(S201F) causes muscular dystrophy and arrhythmia by affecting protein trafficking. J CLIN INVEST. 2016 Jan;126(1):239-53. https://doi.org/10.1172/JCI79562

Bibtex

@article{731f54c83d274e098959f58eb3573823,
title = "POPDC1(S201F) causes muscular dystrophy and arrhythmia by affecting protein trafficking",
abstract = "The Popeye domain-containing 1 (POPDC1) gene encodes a plasma membrane-localized cAMP-binding protein that is abundantly expressed in striated muscle. In animal models, POPDC1 is an essential regulator of structure and function of cardiac and skeletal muscle; however, POPDC1 mutations have not been associated with human cardiac and muscular diseases. Here, we have described a homozygous missense variant (c.602C>T, p.S201F) in POPDC1, identified by whole-exome sequencing, in a family of 4 with cardiac arrhythmia and limb-girdle muscular dystrophy (LGMD). This allele was absent in known databases and segregated with the pathological phenotype in this family. We did not find the allele in a further screen of 104 patients with a similar phenotype, suggesting this mutation to be family specific. Compared with WT protein, POPDC1(S201F) displayed a 50% reduction in cAMP affinity, and in skeletal muscle from patients, both POPDC1(S201F) and WT POPDC2 displayed impaired membrane trafficking. Forced expression of POPDC1(S201F) in a murine cardiac muscle cell line (HL-1) increased hyperpolarization and upstroke velocity of the action potential. In zebrafish, expression of the homologous mutation (popdc1(S191F)) caused heart and skeletal muscle phenotypes that resembled those observed in patients. Our study therefore identifies POPDC1 as a disease gene causing a very rare autosomal recessive cardiac arrhythmia and LGMD, expanding the genetic causes of this heterogeneous group of inherited rare diseases.",
keywords = "Aged, Aged, 80 and over, Animals, Arrhythmias, Cardiac, Child, Cyclic AMP, Humans, Male, Membrane Potentials, Membrane Proteins, Middle Aged, Muscular Dystrophies, Limb-Girdle, Mutation, Potassium Channels, Tandem Pore Domain, Protein Transport, Zebrafish, Journal Article, Research Support, Non-U.S. Gov't",
author = "Schindler, {Roland F R} and Chiara Scotton and Jianguo Zhang and Chiara Passarelli and Beatriz Ortiz-Bonnin and Subreena Simrick and Thorsten Schwerte and Kar-Lai Poon and Mingyan Fang and Susanne Rinn{\'e} and Alexander Froese and Nikolaev, {Viacheslav O} and Christiane Grunert and Thomas M{\"u}ller and Giorgio Tasca and Padmini Sarathchandra and Fabrizio Drago and Bruno Dallapiccola and Claudio Rapezzi and Eloisa Arbustini and {Di Raimo}, {Francesca Romana} and Marcella Neri and Rita Selvatici and Francesca Gualandi and Fabiana Fattori and Antonello Pietrangelo and Wenyan Li and Hui Jiang and Xun Xu and Enrico Bertini and Niels Decher and Jun Wang and Thomas Brand and Alessandra Ferlini",
year = "2016",
month = jan,
doi = "10.1172/JCI79562",
language = "English",
volume = "126",
pages = "239--53",
journal = "J CLIN INVEST",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "1",

}

RIS

TY - JOUR

T1 - POPDC1(S201F) causes muscular dystrophy and arrhythmia by affecting protein trafficking

AU - Schindler, Roland F R

AU - Scotton, Chiara

AU - Zhang, Jianguo

AU - Passarelli, Chiara

AU - Ortiz-Bonnin, Beatriz

AU - Simrick, Subreena

AU - Schwerte, Thorsten

AU - Poon, Kar-Lai

AU - Fang, Mingyan

AU - Rinné, Susanne

AU - Froese, Alexander

AU - Nikolaev, Viacheslav O

AU - Grunert, Christiane

AU - Müller, Thomas

AU - Tasca, Giorgio

AU - Sarathchandra, Padmini

AU - Drago, Fabrizio

AU - Dallapiccola, Bruno

AU - Rapezzi, Claudio

AU - Arbustini, Eloisa

AU - Di Raimo, Francesca Romana

AU - Neri, Marcella

AU - Selvatici, Rita

AU - Gualandi, Francesca

AU - Fattori, Fabiana

AU - Pietrangelo, Antonello

AU - Li, Wenyan

AU - Jiang, Hui

AU - Xu, Xun

AU - Bertini, Enrico

AU - Decher, Niels

AU - Wang, Jun

AU - Brand, Thomas

AU - Ferlini, Alessandra

PY - 2016/1

Y1 - 2016/1

N2 - The Popeye domain-containing 1 (POPDC1) gene encodes a plasma membrane-localized cAMP-binding protein that is abundantly expressed in striated muscle. In animal models, POPDC1 is an essential regulator of structure and function of cardiac and skeletal muscle; however, POPDC1 mutations have not been associated with human cardiac and muscular diseases. Here, we have described a homozygous missense variant (c.602C>T, p.S201F) in POPDC1, identified by whole-exome sequencing, in a family of 4 with cardiac arrhythmia and limb-girdle muscular dystrophy (LGMD). This allele was absent in known databases and segregated with the pathological phenotype in this family. We did not find the allele in a further screen of 104 patients with a similar phenotype, suggesting this mutation to be family specific. Compared with WT protein, POPDC1(S201F) displayed a 50% reduction in cAMP affinity, and in skeletal muscle from patients, both POPDC1(S201F) and WT POPDC2 displayed impaired membrane trafficking. Forced expression of POPDC1(S201F) in a murine cardiac muscle cell line (HL-1) increased hyperpolarization and upstroke velocity of the action potential. In zebrafish, expression of the homologous mutation (popdc1(S191F)) caused heart and skeletal muscle phenotypes that resembled those observed in patients. Our study therefore identifies POPDC1 as a disease gene causing a very rare autosomal recessive cardiac arrhythmia and LGMD, expanding the genetic causes of this heterogeneous group of inherited rare diseases.

AB - The Popeye domain-containing 1 (POPDC1) gene encodes a plasma membrane-localized cAMP-binding protein that is abundantly expressed in striated muscle. In animal models, POPDC1 is an essential regulator of structure and function of cardiac and skeletal muscle; however, POPDC1 mutations have not been associated with human cardiac and muscular diseases. Here, we have described a homozygous missense variant (c.602C>T, p.S201F) in POPDC1, identified by whole-exome sequencing, in a family of 4 with cardiac arrhythmia and limb-girdle muscular dystrophy (LGMD). This allele was absent in known databases and segregated with the pathological phenotype in this family. We did not find the allele in a further screen of 104 patients with a similar phenotype, suggesting this mutation to be family specific. Compared with WT protein, POPDC1(S201F) displayed a 50% reduction in cAMP affinity, and in skeletal muscle from patients, both POPDC1(S201F) and WT POPDC2 displayed impaired membrane trafficking. Forced expression of POPDC1(S201F) in a murine cardiac muscle cell line (HL-1) increased hyperpolarization and upstroke velocity of the action potential. In zebrafish, expression of the homologous mutation (popdc1(S191F)) caused heart and skeletal muscle phenotypes that resembled those observed in patients. Our study therefore identifies POPDC1 as a disease gene causing a very rare autosomal recessive cardiac arrhythmia and LGMD, expanding the genetic causes of this heterogeneous group of inherited rare diseases.

KW - Aged

KW - Aged, 80 and over

KW - Animals

KW - Arrhythmias, Cardiac

KW - Child

KW - Cyclic AMP

KW - Humans

KW - Male

KW - Membrane Potentials

KW - Membrane Proteins

KW - Middle Aged

KW - Muscular Dystrophies, Limb-Girdle

KW - Mutation

KW - Potassium Channels, Tandem Pore Domain

KW - Protein Transport

KW - Zebrafish

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1172/JCI79562

DO - 10.1172/JCI79562

M3 - SCORING: Journal article

C2 - 26642364

VL - 126

SP - 239

EP - 253

JO - J CLIN INVEST

JF - J CLIN INVEST

SN - 0021-9738

IS - 1

ER -