PortalPublikationenParalog Studies Augment Gene Discovery: DDX and DHX Genes

Paralog Studies Augment Gene Discovery: DDX and DHX Genes

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Paralog Studies Augment Gene Discovery: DDX and DHX Genes. / Paine, Ingrid; Posey, Jennifer E; Grochowski, Christopher M; Jhangiani, Shalini N; Rosenheck, Sarah; Kleyner, Robert; Marmorale, Taylor; Yoon, Margaret; Wang, Kai; Robison, Reid; Cappuccio, Gerarda; Pinelli, Michele; Magli, Adriano; Coban Akdemir, Zeynep; Hui, Joannie; Yeung, Wai Lan; Wong, Bibiana K Y; Ortega, Lucia; Bekheirnia, Mir Reza; Bierhals, Tatjana; Hempel, Maja; Johannsen, Jessika; Santer, René; Aktas, Dilek; Alikasifoglu, Mehmet; Bozdogan, Sevcan; Aydin, Hatip; Karaca, Ender; Bayram, Yavuz; Ityel, Hadas; Dorschner, Michael; White, Janson J; Wilichowski, Ekkehard; Wortmann, Saskia B; Casella, Erasmo B; Kitajima, Joao Paulo; Kok, Fernando; Monteiro, Fabiola; Muzny, Donna M; Bamshad, Michael; Gibbs, Richard A; Sutton, V Reid; University of Washington Center for Mendelian Genomics, Baylor-Hopkins Center for Mendelian Genomics, Telethon Undiagnosed Diseases Program; Van Esch, Hilde; Brunetti-Pierri, Nicola; Hildebrandt, Friedhelm; Brautbar, Ariel; Van den Veyver, Ignatia B; Glass, Ian; Lessel, Davor; Lyon, Gholson J; Lupski, James R.

in: AM J HUM GENET, Jahrgang 105, Nr. 2, 01.08.2019, S. 302-316.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Paine, I, Posey, JE, Grochowski, CM, Jhangiani, SN, Rosenheck, S, Kleyner, R, Marmorale, T, Yoon, M, Wang, K, Robison, R, Cappuccio, G, Pinelli, M, Magli, A, Coban Akdemir, Z, Hui, J, Yeung, WL, Wong, BKY, Ortega, L, Bekheirnia, MR, Bierhals, T, Hempel, M, Johannsen, J, Santer, R, Aktas, D, Alikasifoglu, M, Bozdogan, S, Aydin, H, Karaca, E, Bayram, Y, Ityel, H, Dorschner, M, White, JJ, Wilichowski, E, Wortmann, SB, Casella, EB, Kitajima, JP, Kok, F, Monteiro, F, Muzny, DM, Bamshad, M, Gibbs, RA, Sutton, VR, University of Washington Center for Mendelian Genomics, Baylor-Hopkins Center for Mendelian Genomics, Telethon Undiagnosed Diseases Program, Van Esch, H, Brunetti-Pierri, N, Hildebrandt, F, Brautbar, A, Van den Veyver, IB, Glass, I, Lessel, D, Lyon, GJ & Lupski, JR 2019, 'Paralog Studies Augment Gene Discovery: DDX and DHX Genes', AM J HUM GENET, Jg. 105, Nr. 2, S. 302-316. https://doi.org/10.1016/j.ajhg.2019.06.001

APA

Paine, I., Posey, J. E., Grochowski, C. M., Jhangiani, S. N., Rosenheck, S., Kleyner, R., Marmorale, T., Yoon, M., Wang, K., Robison, R., Cappuccio, G., Pinelli, M., Magli, A., Coban Akdemir, Z., Hui, J., Yeung, W. L., Wong, B. K. Y., Ortega, L., Bekheirnia, M. R., ... Lupski, J. R. (2019). Paralog Studies Augment Gene Discovery: DDX and DHX Genes. AM J HUM GENET, 105(2), 302-316. https://doi.org/10.1016/j.ajhg.2019.06.001

Vancouver

Paine I, Posey JE, Grochowski CM, Jhangiani SN, Rosenheck S, Kleyner R et al. Paralog Studies Augment Gene Discovery: DDX and DHX Genes. AM J HUM GENET. 2019 Aug 1;105(2):302-316. https://doi.org/10.1016/j.ajhg.2019.06.001

Bibtex

@article{7630e280b01544e8b1e08aec97a3c075,
title = "Paralog Studies Augment Gene Discovery: DDX and DHX Genes",
abstract = "Members of a paralogous gene family in which variation in one gene is known to cause disease are eight times more likely to also be associated with human disease. Recent studies have elucidated DHX30 and DDX3X as genes for which pathogenic variant alleles are involved in neurodevelopmental disorders. We hypothesized that variants in paralogous genes encoding members of the DExD/H-box RNA helicase superfamily might also underlie developmental delay and/or intellectual disability (DD and/or ID) disease phenotypes. Here we describe 15 unrelated individuals who have DD and/or ID, central nervous system (CNS) dysfunction, vertebral anomalies, and dysmorphic features and were found to have probably damaging variants in DExD/H-box RNA helicase genes. In addition, these individuals exhibit a variety of other tissue and organ system involvement including ocular, outer ear, hearing, cardiac, and kidney tissues. Five individuals with homozygous (one), compound-heterozygous (two), or de novo (two) missense variants in DHX37 were identified by exome sequencing. We identified ten total individuals with missense variants in three other DDX/DHX paralogs: DHX16 (four individuals), DDX54 (three individuals), and DHX34 (three individuals). Most identified variants are rare, predicted to be damaging, and occur at conserved amino acid residues. Taken together, these 15 individuals implicate the DExD/H-box helicases in both dominantly and recessively inherited neurodevelopmental phenotypes and highlight the potential for more than one disease mechanism underlying these disorders.",
author = "Ingrid Paine and Posey, {Jennifer E} and Grochowski, {Christopher M} and Jhangiani, {Shalini N} and Sarah Rosenheck and Robert Kleyner and Taylor Marmorale and Margaret Yoon and Kai Wang and Reid Robison and Gerarda Cappuccio and Michele Pinelli and Adriano Magli and {Coban Akdemir}, Zeynep and Joannie Hui and Yeung, {Wai Lan} and Wong, {Bibiana K Y} and Lucia Ortega and Bekheirnia, {Mir Reza} and Tatjana Bierhals and Maja Hempel and Jessika Johannsen and Ren{\'e} Santer and Dilek Aktas and Mehmet Alikasifoglu and Sevcan Bozdogan and Hatip Aydin and Ender Karaca and Yavuz Bayram and Hadas Ityel and Michael Dorschner and White, {Janson J} and Ekkehard Wilichowski and Wortmann, {Saskia B} and Casella, {Erasmo B} and Kitajima, {Joao Paulo} and Fernando Kok and Fabiola Monteiro and Muzny, {Donna M} and Michael Bamshad and Gibbs, {Richard A} and Sutton, {V Reid} and {University of Washington Center for Mendelian Genomics, Baylor-Hopkins Center for Mendelian Genomics, Telethon Undiagnosed Diseases Program} and {Van Esch}, Hilde and Nicola Brunetti-Pierri and Friedhelm Hildebrandt and Ariel Brautbar and {Van den Veyver}, {Ignatia B} and Ian Glass and Davor Lessel and Lyon, {Gholson J} and Lupski, {James R}",
note = "Copyright {\textcopyright} 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.",
year = "2019",
month = aug,
day = "1",
doi = "10.1016/j.ajhg.2019.06.001",
language = "English",
volume = "105",
pages = "302--316",
journal = "AM J HUM GENET",
issn = "0002-9297",
publisher = "Cell Press",
number = "2",

}

RIS

TY - JOUR

T1 - Paralog Studies Augment Gene Discovery: DDX and DHX Genes

AU - Paine, Ingrid

AU - Posey, Jennifer E

AU - Grochowski, Christopher M

AU - Jhangiani, Shalini N

AU - Rosenheck, Sarah

AU - Kleyner, Robert

AU - Marmorale, Taylor

AU - Yoon, Margaret

AU - Wang, Kai

AU - Robison, Reid

AU - Cappuccio, Gerarda

AU - Pinelli, Michele

AU - Magli, Adriano

AU - Coban Akdemir, Zeynep

AU - Hui, Joannie

AU - Yeung, Wai Lan

AU - Wong, Bibiana K Y

AU - Ortega, Lucia

AU - Bekheirnia, Mir Reza

AU - Bierhals, Tatjana

AU - Hempel, Maja

AU - Johannsen, Jessika

AU - Santer, René

AU - Aktas, Dilek

AU - Alikasifoglu, Mehmet

AU - Bozdogan, Sevcan

AU - Aydin, Hatip

AU - Karaca, Ender

AU - Bayram, Yavuz

AU - Ityel, Hadas

AU - Dorschner, Michael

AU - White, Janson J

AU - Wilichowski, Ekkehard

AU - Wortmann, Saskia B

AU - Casella, Erasmo B

AU - Kitajima, Joao Paulo

AU - Kok, Fernando

AU - Monteiro, Fabiola

AU - Muzny, Donna M

AU - Bamshad, Michael

AU - Gibbs, Richard A

AU - Sutton, V Reid

AU - University of Washington Center for Mendelian Genomics, Baylor-Hopkins Center for Mendelian Genomics, Telethon Undiagnosed Diseases Program

AU - Van Esch, Hilde

AU - Brunetti-Pierri, Nicola

AU - Hildebrandt, Friedhelm

AU - Brautbar, Ariel

AU - Van den Veyver, Ignatia B

AU - Glass, Ian

AU - Lessel, Davor

AU - Lyon, Gholson J

AU - Lupski, James R

N1 - Copyright © 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

PY - 2019/8/1

Y1 - 2019/8/1

N2 - Members of a paralogous gene family in which variation in one gene is known to cause disease are eight times more likely to also be associated with human disease. Recent studies have elucidated DHX30 and DDX3X as genes for which pathogenic variant alleles are involved in neurodevelopmental disorders. We hypothesized that variants in paralogous genes encoding members of the DExD/H-box RNA helicase superfamily might also underlie developmental delay and/or intellectual disability (DD and/or ID) disease phenotypes. Here we describe 15 unrelated individuals who have DD and/or ID, central nervous system (CNS) dysfunction, vertebral anomalies, and dysmorphic features and were found to have probably damaging variants in DExD/H-box RNA helicase genes. In addition, these individuals exhibit a variety of other tissue and organ system involvement including ocular, outer ear, hearing, cardiac, and kidney tissues. Five individuals with homozygous (one), compound-heterozygous (two), or de novo (two) missense variants in DHX37 were identified by exome sequencing. We identified ten total individuals with missense variants in three other DDX/DHX paralogs: DHX16 (four individuals), DDX54 (three individuals), and DHX34 (three individuals). Most identified variants are rare, predicted to be damaging, and occur at conserved amino acid residues. Taken together, these 15 individuals implicate the DExD/H-box helicases in both dominantly and recessively inherited neurodevelopmental phenotypes and highlight the potential for more than one disease mechanism underlying these disorders.

AB - Members of a paralogous gene family in which variation in one gene is known to cause disease are eight times more likely to also be associated with human disease. Recent studies have elucidated DHX30 and DDX3X as genes for which pathogenic variant alleles are involved in neurodevelopmental disorders. We hypothesized that variants in paralogous genes encoding members of the DExD/H-box RNA helicase superfamily might also underlie developmental delay and/or intellectual disability (DD and/or ID) disease phenotypes. Here we describe 15 unrelated individuals who have DD and/or ID, central nervous system (CNS) dysfunction, vertebral anomalies, and dysmorphic features and were found to have probably damaging variants in DExD/H-box RNA helicase genes. In addition, these individuals exhibit a variety of other tissue and organ system involvement including ocular, outer ear, hearing, cardiac, and kidney tissues. Five individuals with homozygous (one), compound-heterozygous (two), or de novo (two) missense variants in DHX37 were identified by exome sequencing. We identified ten total individuals with missense variants in three other DDX/DHX paralogs: DHX16 (four individuals), DDX54 (three individuals), and DHX34 (three individuals). Most identified variants are rare, predicted to be damaging, and occur at conserved amino acid residues. Taken together, these 15 individuals implicate the DExD/H-box helicases in both dominantly and recessively inherited neurodevelopmental phenotypes and highlight the potential for more than one disease mechanism underlying these disorders.

U2 - 10.1016/j.ajhg.2019.06.001

DO - 10.1016/j.ajhg.2019.06.001

M3 - SCORING: Journal article

C2 - 31256877

VL - 105

SP - 302

EP - 316

JO - AM J HUM GENET

JF - AM J HUM GENET

SN - 0002-9297

IS - 2

ER -