Publication

A mutation update for the FLNC gene in myopathies and cardiomyopathies

Verdonschot, J. A. J., Vanhoutte, E. K., Claes, G. R. F., van den Enden, A. T. J. M. H., Hoeijmakers, J. G. J., Hellebrekers, D. M. E. I., Haan, A. D., Christiaans, I., Deprez, R. H. L., Boen, H. M., Craenenbroeck, E. M. V., Loeys, B. L., Hoedemaekers, Y. M., Marcelis, C., Kempers, M., Brusse, E., Waning, J. I., Baas, A. F., Dooijes, D., Asselbergs, F. W., Barge-Schaapveld, D. Q. C. M., Koopman, P., Wijngaard, A. V. D., Heymans, S. R. B., Krapels, I. P. C. & Brunner, H. G., Jun-2020, In : Human Mutation. 41, 6, p. 1091-1111 21 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Verdonschot, J. A. J., Vanhoutte, E. K., Claes, G. R. F., van den Enden, A. T. J. M. H., Hoeijmakers, J. G. J., Hellebrekers, D. M. E. I., Haan, A. D., Christiaans, I., Deprez, R. H. L., Boen, H. M., Craenenbroeck, E. M. V., Loeys, B. L., Hoedemaekers, Y. M., Marcelis, C., Kempers, M., Brusse, E., Waning, J. I., Baas, A. F., Dooijes, D., ... Brunner, H. G. (2020). A mutation update for the FLNC gene in myopathies and cardiomyopathies. Human Mutation, 41(6), 1091-1111. https://doi.org/10.1002/humu.24004

Author

Verdonschot, Job A. J. ; Vanhoutte, Els K. ; Claes, Godelieve R. F. ; van den Enden, Apollonia T. J. M. Helderman ; Hoeijmakers, Janneke G. J. ; Hellebrekers, Debby M. E. I. ; Haan, Amber de ; Christiaans, Imke ; Deprez, Ronald H. Lekanne ; Boen, Hanne M. ; Craenenbroeck, Emeline M. van ; Loeys, Bart L. ; Hoedemaekers, Yvonne M. ; Marcelis, Carlo ; Kempers, Marlies ; Brusse, Esther ; Waning, Jaap I. ; Baas, Annette F. ; Dooijes, Dennis ; Asselbergs, Folkert W. ; Barge-Schaapveld, Daniela Q. C. M. ; Koopman, Pieter ; Wijngaard, Arthur van den ; Heymans, Stephane R. B. ; Krapels, Ingrid P. C. ; Brunner, Han G. / A mutation update for the FLNC gene in myopathies and cardiomyopathies. In: Human Mutation. 2020 ; Vol. 41, No. 6. pp. 1091-1111.

Harvard

Verdonschot, JAJ, Vanhoutte, EK, Claes, GRF, van den Enden, ATJMH, Hoeijmakers, JGJ, Hellebrekers, DMEI, Haan, AD, Christiaans, I, Deprez, RHL, Boen, HM, Craenenbroeck, EMV, Loeys, BL, Hoedemaekers, YM, Marcelis, C, Kempers, M, Brusse, E, Waning, JI, Baas, AF, Dooijes, D, Asselbergs, FW, Barge-Schaapveld, DQCM, Koopman, P, Wijngaard, AVD, Heymans, SRB, Krapels, IPC & Brunner, HG 2020, 'A mutation update for the FLNC gene in myopathies and cardiomyopathies', Human Mutation, vol. 41, no. 6, pp. 1091-1111. https://doi.org/10.1002/humu.24004

Standard

A mutation update for the FLNC gene in myopathies and cardiomyopathies. / Verdonschot, Job A. J.; Vanhoutte, Els K.; Claes, Godelieve R. F.; van den Enden, Apollonia T. J. M. Helderman; Hoeijmakers, Janneke G. J.; Hellebrekers, Debby M. E. I.; Haan, Amber de; Christiaans, Imke; Deprez, Ronald H. Lekanne; Boen, Hanne M.; Craenenbroeck, Emeline M. van; Loeys, Bart L.; Hoedemaekers, Yvonne M.; Marcelis, Carlo; Kempers, Marlies; Brusse, Esther; Waning, Jaap I.; Baas, Annette F.; Dooijes, Dennis; Asselbergs, Folkert W.; Barge-Schaapveld, Daniela Q. C. M.; Koopman, Pieter; Wijngaard, Arthur van den; Heymans, Stephane R. B.; Krapels, Ingrid P. C.; Brunner, Han G.

In: Human Mutation, Vol. 41, No. 6, 06.2020, p. 1091-1111.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Verdonschot JAJ, Vanhoutte EK, Claes GRF, van den Enden ATJMH, Hoeijmakers JGJ, Hellebrekers DMEI et al. A mutation update for the FLNC gene in myopathies and cardiomyopathies. Human Mutation. 2020 Jun;41(6):1091-1111. https://doi.org/10.1002/humu.24004


BibTeX

@article{a89a38f04148437d984390704349c960,
title = "A mutation update for the FLNC gene in myopathies and cardiomyopathies",
abstract = "Filamin C (FLNC) variants are associated with cardiac and muscular phenotypes. Originally, FLNC variants were described in myofibrillar myopathy (MFM) patients. Later, high-throughput screening in cardiomyopathy cohorts determined a prominent role for FLNC in isolated hypertrophic and dilated cardiomyopathies (HCM and DCM). FLNC variants are now among the more prevalent causes of genetic DCM. FLNC-associated DCM is associated with a malignant clinical course and a high risk of sudden cardiac death. The clinical spectrum of FLNC suggests different pathomechanisms related to variant types and their location in the gene. The appropriate functioning of FLNC is crucial for structural integrity and cell signaling of the sarcomere. The secondary protein structure of FLNC is critical to ensure this function. Truncating variants with subsequent haploinsufficiency are associated with DCM and cardiac arrhythmias. Interference with the dimerization and folding of the protein leads to aggregate formation detrimental for muscle function, as found in HCM and MFM. Variants associated with HCM are predominantly missense variants, which cluster in the ROD2 domain. This domain is important for binding to the sarcomere and to ensure appropriate cell signaling. We here review FLNC genotype-phenotype correlations based on available evidence.",
keywords = "cardiomyopathy, filamin, FLNC, genotype-phenotype correlation, myopathy, ACTIN-BINDING DOMAIN, FILAMIN-C, MYOFIBRILLAR MYOPATHY, HYPERTROPHIC CARDIOMYOPATHY, TRUNCATING VARIANTS, PROTEIN AGGREGATION, MUSCULAR-DYSTROPHY, HEART-FAILURE, CLASSIFICATION, IDENTIFICATION",
author = "Verdonschot, {Job A. J.} and Vanhoutte, {Els K.} and Claes, {Godelieve R. F.} and {van den Enden}, {Apollonia T. J. M. Helderman} and Hoeijmakers, {Janneke G. J.} and Hellebrekers, {Debby M. E. I.} and Haan, {Amber de} and Imke Christiaans and Deprez, {Ronald H. Lekanne} and Boen, {Hanne M.} and Craenenbroeck, {Emeline M. van} and Loeys, {Bart L.} and Hoedemaekers, {Yvonne M.} and Carlo Marcelis and Marlies Kempers and Esther Brusse and Waning, {Jaap I.} and Baas, {Annette F.} and Dennis Dooijes and Asselbergs, {Folkert W.} and Barge-Schaapveld, {Daniela Q. C. M.} and Pieter Koopman and Wijngaard, {Arthur van den} and Heymans, {Stephane R. B.} and Krapels, {Ingrid P. C.} and Brunner, {Han G.}",
year = "2020",
month = jun,
doi = "10.1002/humu.24004",
language = "English",
volume = "41",
pages = "1091--1111",
journal = "Human Mutation",
issn = "1059-7794",
publisher = "Wiley",
number = "6",

}

RIS

TY - JOUR

T1 - A mutation update for the FLNC gene in myopathies and cardiomyopathies

AU - Verdonschot, Job A. J.

AU - Vanhoutte, Els K.

AU - Claes, Godelieve R. F.

AU - van den Enden, Apollonia T. J. M. Helderman

AU - Hoeijmakers, Janneke G. J.

AU - Hellebrekers, Debby M. E. I.

AU - Haan, Amber de

AU - Christiaans, Imke

AU - Deprez, Ronald H. Lekanne

AU - Boen, Hanne M.

AU - Craenenbroeck, Emeline M. van

AU - Loeys, Bart L.

AU - Hoedemaekers, Yvonne M.

AU - Marcelis, Carlo

AU - Kempers, Marlies

AU - Brusse, Esther

AU - Waning, Jaap I.

AU - Baas, Annette F.

AU - Dooijes, Dennis

AU - Asselbergs, Folkert W.

AU - Barge-Schaapveld, Daniela Q. C. M.

AU - Koopman, Pieter

AU - Wijngaard, Arthur van den

AU - Heymans, Stephane R. B.

AU - Krapels, Ingrid P. C.

AU - Brunner, Han G.

PY - 2020/6

Y1 - 2020/6

N2 - Filamin C (FLNC) variants are associated with cardiac and muscular phenotypes. Originally, FLNC variants were described in myofibrillar myopathy (MFM) patients. Later, high-throughput screening in cardiomyopathy cohorts determined a prominent role for FLNC in isolated hypertrophic and dilated cardiomyopathies (HCM and DCM). FLNC variants are now among the more prevalent causes of genetic DCM. FLNC-associated DCM is associated with a malignant clinical course and a high risk of sudden cardiac death. The clinical spectrum of FLNC suggests different pathomechanisms related to variant types and their location in the gene. The appropriate functioning of FLNC is crucial for structural integrity and cell signaling of the sarcomere. The secondary protein structure of FLNC is critical to ensure this function. Truncating variants with subsequent haploinsufficiency are associated with DCM and cardiac arrhythmias. Interference with the dimerization and folding of the protein leads to aggregate formation detrimental for muscle function, as found in HCM and MFM. Variants associated with HCM are predominantly missense variants, which cluster in the ROD2 domain. This domain is important for binding to the sarcomere and to ensure appropriate cell signaling. We here review FLNC genotype-phenotype correlations based on available evidence.

AB - Filamin C (FLNC) variants are associated with cardiac and muscular phenotypes. Originally, FLNC variants were described in myofibrillar myopathy (MFM) patients. Later, high-throughput screening in cardiomyopathy cohorts determined a prominent role for FLNC in isolated hypertrophic and dilated cardiomyopathies (HCM and DCM). FLNC variants are now among the more prevalent causes of genetic DCM. FLNC-associated DCM is associated with a malignant clinical course and a high risk of sudden cardiac death. The clinical spectrum of FLNC suggests different pathomechanisms related to variant types and their location in the gene. The appropriate functioning of FLNC is crucial for structural integrity and cell signaling of the sarcomere. The secondary protein structure of FLNC is critical to ensure this function. Truncating variants with subsequent haploinsufficiency are associated with DCM and cardiac arrhythmias. Interference with the dimerization and folding of the protein leads to aggregate formation detrimental for muscle function, as found in HCM and MFM. Variants associated with HCM are predominantly missense variants, which cluster in the ROD2 domain. This domain is important for binding to the sarcomere and to ensure appropriate cell signaling. We here review FLNC genotype-phenotype correlations based on available evidence.

KW - cardiomyopathy

KW - filamin

KW - FLNC

KW - genotype-phenotype correlation

KW - myopathy

KW - ACTIN-BINDING DOMAIN

KW - FILAMIN-C

KW - MYOFIBRILLAR MYOPATHY

KW - HYPERTROPHIC CARDIOMYOPATHY

KW - TRUNCATING VARIANTS

KW - PROTEIN AGGREGATION

KW - MUSCULAR-DYSTROPHY

KW - HEART-FAILURE

KW - CLASSIFICATION

KW - IDENTIFICATION

U2 - 10.1002/humu.24004

DO - 10.1002/humu.24004

M3 - Article

VL - 41

SP - 1091

EP - 1111

JO - Human Mutation

JF - Human Mutation

SN - 1059-7794

IS - 6

ER -

ID: 135024161