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Etiological involvement of KCND1 variants in an X-linked neurodevelopmental disorder with variable expressivity

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Etiological involvement of KCND1 variants in an X-linked neurodevelopmental disorder with variable expressivity. / Kalm, Tassja; Schob, Claudia; Völler, Hanna; Gardeitchik, Thatjana; Gilissen, Christian; Pfundt, Rolph; Klöckner, Chiara; Platzer, Konrad; Klabunde-Cherwon, Annick; Ries, Markus; Syrbe, Steffen; Beccaria, Francesca; Madia, Francesca; Scala, Marcello; Zara, Federico; Hofstede, Floris; Simon, Marleen E H; van Jaarsveld, Richard H; Oegema, Renske; van Gassen, Koen L I; Holwerda, Sjoerd J B; Barakat, Tahsin Stefan; Bouman, Arjan; van Slegtenhorst, Marjon; Álvarez, Sara; Fernández-Jaén, Alberto; Porta, Javier; Accogli, Andrea; Mancardi, Margherita Maria; Striano, Pasquale; Iacomino, Michele; Chae, Jong-Hee; Jang, SeSong; Kim, Soo Y; Chitayat, David; Mercimek-Andrews, Saadet; Depienne, Christel; Kampmeier, Antje; Kuechler, Alma; Surowy, Harald; Bertini, Enrico Silvio; Radio, Francesca Clementina; Mancini, Cecilia; Pizzi, Simone; Tartaglia, Marco; Gauthier, Lucas; Genevieve, David; Tharreau, Mylène; Azoulay, Noy; Zaks-Hoffer, Gal; Gilad, Nesia K; Orenstein, Naama; Bernard, Geneviève; Thiffault, Isabelle; Denecke, Jonas; Herget, Theresia; Kortüm, Fanny; Kubisch, Christian; Bähring, Robert; Kindler, Stefan.

In: AM J HUM GENET, Vol. 111, No. 6, 06.06.2024, p. 1206-1221.

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

Harvard

Kalm, T, Schob, C, Völler, H, Gardeitchik, T, Gilissen, C, Pfundt, R, Klöckner, C, Platzer, K, Klabunde-Cherwon, A, Ries, M, Syrbe, S, Beccaria, F, Madia, F, Scala, M, Zara, F, Hofstede, F, Simon, MEH, van Jaarsveld, RH, Oegema, R, van Gassen, KLI, Holwerda, SJB, Barakat, TS, Bouman, A, van Slegtenhorst, M, Álvarez, S, Fernández-Jaén, A, Porta, J, Accogli, A, Mancardi, MM, Striano, P, Iacomino, M, Chae, J-H, Jang, S, Kim, SY, Chitayat, D, Mercimek-Andrews, S, Depienne, C, Kampmeier, A, Kuechler, A, Surowy, H, Bertini, ES, Radio, FC, Mancini, C, Pizzi, S, Tartaglia, M, Gauthier, L, Genevieve, D, Tharreau, M, Azoulay, N, Zaks-Hoffer, G, Gilad, NK, Orenstein, N, Bernard, G, Thiffault, I, Denecke, J, Herget, T, Kortüm, F, Kubisch, C, Bähring, R & Kindler, S 2024, 'Etiological involvement of KCND1 variants in an X-linked neurodevelopmental disorder with variable expressivity', AM J HUM GENET, vol. 111, no. 6, pp. 1206-1221. https://doi.org/10.1016/j.ajhg.2024.04.019

APA

Kalm, T., Schob, C., Völler, H., Gardeitchik, T., Gilissen, C., Pfundt, R., Klöckner, C., Platzer, K., Klabunde-Cherwon, A., Ries, M., Syrbe, S., Beccaria, F., Madia, F., Scala, M., Zara, F., Hofstede, F., Simon, M. E. H., van Jaarsveld, R. H., Oegema, R., ... Kindler, S. (2024). Etiological involvement of KCND1 variants in an X-linked neurodevelopmental disorder with variable expressivity. AM J HUM GENET, 111(6), 1206-1221. https://doi.org/10.1016/j.ajhg.2024.04.019

Vancouver

Kalm T, Schob C, Völler H, Gardeitchik T, Gilissen C, Pfundt R et al. Etiological involvement of KCND1 variants in an X-linked neurodevelopmental disorder with variable expressivity. AM J HUM GENET. 2024 Jun 6;111(6):1206-1221. https://doi.org/10.1016/j.ajhg.2024.04.019

Bibtex

@article{5e178d1fcb594aba9ddeb4d0fd803e74,
title = "Etiological involvement of KCND1 variants in an X-linked neurodevelopmental disorder with variable expressivity",
abstract = "Utilizing trio whole-exome sequencing and a gene matching approach, we identified a cohort of 18 male individuals from 17 families with hemizygous variants in KCND1, including two de novo missense variants, three maternally inherited protein-truncating variants, and 12 maternally inherited missense variants. Affected subjects present with a neurodevelopmental disorder characterized by diverse neurological abnormalities, mostly delays in different developmental domains, but also distinct neuropsychiatric signs and epilepsy. Heterozygous carrier mothers are clinically unaffected. KCND1 encodes the α-subunit of Kv4.1 voltage-gated potassium channels. All variant-associated amino acid substitutions affect either the cytoplasmic N- or C-terminus of the channel protein except for two occurring in transmembrane segments 1 and 4. Kv4.1 channels were functionally characterized in the absence and presence of auxiliary β subunits. Variant-specific alterations of biophysical channel properties were diverse and varied in magnitude. Genetic data analysis in combination with our functional assessment shows that Kv4.1 channel dysfunction is involved in the pathogenesis of an X-linked neurodevelopmental disorder frequently associated with a variable neuropsychiatric clinical phenotype.",
author = "Tassja Kalm and Claudia Schob and Hanna V{\"o}ller and Thatjana Gardeitchik and Christian Gilissen and Rolph Pfundt and Chiara Kl{\"o}ckner and Konrad Platzer and Annick Klabunde-Cherwon and Markus Ries and Steffen Syrbe and Francesca Beccaria and Francesca Madia and Marcello Scala and Federico Zara and Floris Hofstede and Simon, {Marleen E H} and {van Jaarsveld}, {Richard H} and Renske Oegema and {van Gassen}, {Koen L I} and Holwerda, {Sjoerd J B} and Barakat, {Tahsin Stefan} and Arjan Bouman and {van Slegtenhorst}, Marjon and Sara {\'A}lvarez and Alberto Fern{\'a}ndez-Ja{\'e}n and Javier Porta and Andrea Accogli and Mancardi, {Margherita Maria} and Pasquale Striano and Michele Iacomino and Jong-Hee Chae and SeSong Jang and Kim, {Soo Y} and David Chitayat and Saadet Mercimek-Andrews and Christel Depienne and Antje Kampmeier and Alma Kuechler and Harald Surowy and Bertini, {Enrico Silvio} and Radio, {Francesca Clementina} and Cecilia Mancini and Simone Pizzi and Marco Tartaglia and Lucas Gauthier and David Genevieve and Myl{\`e}ne Tharreau and Noy Azoulay and Gal Zaks-Hoffer and Gilad, {Nesia K} and Naama Orenstein and Genevi{\`e}ve Bernard and Isabelle Thiffault and Jonas Denecke and Theresia Herget and Fanny Kort{\"u}m and Christian Kubisch and Robert B{\"a}hring and Stefan Kindler",
note = "Copyright {\textcopyright} 2024 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2024",
month = jun,
day = "6",
doi = "10.1016/j.ajhg.2024.04.019",
language = "English",
volume = "111",
pages = "1206--1221",
journal = "AM J HUM GENET",
issn = "0002-9297",
publisher = "Cell Press",
number = "6",

}

RIS

TY - JOUR

T1 - Etiological involvement of KCND1 variants in an X-linked neurodevelopmental disorder with variable expressivity

AU - Kalm, Tassja

AU - Schob, Claudia

AU - Völler, Hanna

AU - Gardeitchik, Thatjana

AU - Gilissen, Christian

AU - Pfundt, Rolph

AU - Klöckner, Chiara

AU - Platzer, Konrad

AU - Klabunde-Cherwon, Annick

AU - Ries, Markus

AU - Syrbe, Steffen

AU - Beccaria, Francesca

AU - Madia, Francesca

AU - Scala, Marcello

AU - Zara, Federico

AU - Hofstede, Floris

AU - Simon, Marleen E H

AU - van Jaarsveld, Richard H

AU - Oegema, Renske

AU - van Gassen, Koen L I

AU - Holwerda, Sjoerd J B

AU - Barakat, Tahsin Stefan

AU - Bouman, Arjan

AU - van Slegtenhorst, Marjon

AU - Álvarez, Sara

AU - Fernández-Jaén, Alberto

AU - Porta, Javier

AU - Accogli, Andrea

AU - Mancardi, Margherita Maria

AU - Striano, Pasquale

AU - Iacomino, Michele

AU - Chae, Jong-Hee

AU - Jang, SeSong

AU - Kim, Soo Y

AU - Chitayat, David

AU - Mercimek-Andrews, Saadet

AU - Depienne, Christel

AU - Kampmeier, Antje

AU - Kuechler, Alma

AU - Surowy, Harald

AU - Bertini, Enrico Silvio

AU - Radio, Francesca Clementina

AU - Mancini, Cecilia

AU - Pizzi, Simone

AU - Tartaglia, Marco

AU - Gauthier, Lucas

AU - Genevieve, David

AU - Tharreau, Mylène

AU - Azoulay, Noy

AU - Zaks-Hoffer, Gal

AU - Gilad, Nesia K

AU - Orenstein, Naama

AU - Bernard, Geneviève

AU - Thiffault, Isabelle

AU - Denecke, Jonas

AU - Herget, Theresia

AU - Kortüm, Fanny

AU - Kubisch, Christian

AU - Bähring, Robert

AU - Kindler, Stefan

N1 - Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2024/6/6

Y1 - 2024/6/6

N2 - Utilizing trio whole-exome sequencing and a gene matching approach, we identified a cohort of 18 male individuals from 17 families with hemizygous variants in KCND1, including two de novo missense variants, three maternally inherited protein-truncating variants, and 12 maternally inherited missense variants. Affected subjects present with a neurodevelopmental disorder characterized by diverse neurological abnormalities, mostly delays in different developmental domains, but also distinct neuropsychiatric signs and epilepsy. Heterozygous carrier mothers are clinically unaffected. KCND1 encodes the α-subunit of Kv4.1 voltage-gated potassium channels. All variant-associated amino acid substitutions affect either the cytoplasmic N- or C-terminus of the channel protein except for two occurring in transmembrane segments 1 and 4. Kv4.1 channels were functionally characterized in the absence and presence of auxiliary β subunits. Variant-specific alterations of biophysical channel properties were diverse and varied in magnitude. Genetic data analysis in combination with our functional assessment shows that Kv4.1 channel dysfunction is involved in the pathogenesis of an X-linked neurodevelopmental disorder frequently associated with a variable neuropsychiatric clinical phenotype.

AB - Utilizing trio whole-exome sequencing and a gene matching approach, we identified a cohort of 18 male individuals from 17 families with hemizygous variants in KCND1, including two de novo missense variants, three maternally inherited protein-truncating variants, and 12 maternally inherited missense variants. Affected subjects present with a neurodevelopmental disorder characterized by diverse neurological abnormalities, mostly delays in different developmental domains, but also distinct neuropsychiatric signs and epilepsy. Heterozygous carrier mothers are clinically unaffected. KCND1 encodes the α-subunit of Kv4.1 voltage-gated potassium channels. All variant-associated amino acid substitutions affect either the cytoplasmic N- or C-terminus of the channel protein except for two occurring in transmembrane segments 1 and 4. Kv4.1 channels were functionally characterized in the absence and presence of auxiliary β subunits. Variant-specific alterations of biophysical channel properties were diverse and varied in magnitude. Genetic data analysis in combination with our functional assessment shows that Kv4.1 channel dysfunction is involved in the pathogenesis of an X-linked neurodevelopmental disorder frequently associated with a variable neuropsychiatric clinical phenotype.

U2 - 10.1016/j.ajhg.2024.04.019

DO - 10.1016/j.ajhg.2024.04.019

M3 - SCORING: Journal article

C2 - 38772379

VL - 111

SP - 1206

EP - 1221

JO - AM J HUM GENET

JF - AM J HUM GENET

SN - 0002-9297

IS - 6

ER -