Recurrent ATP1A1 variant Gly903Arg causes developmental delay, intellectual disability, and autism

Undiagnosed Diseases Network; Maike F. Dohrn; Guney Bademci; Adriana P. Rebelo; Médéric Jeanne; Nicholas A. Borja; Danique Beijer; Matt C. Danzi; Stephanie A. Bivona; Paul Gueguen; Mohammad F. Zafeer; Mustafa Tekin; Stephan Züchner; Maria T. Acosta; David R. Adams; Ben Afzali; Aimee Allworth; Raquel L. Alvarez; Justin Alvey; Ashley Andrews; Euan A. Ashley; Carlos A. Bacino; Ashok Balasubramanyam; Dustin Baldridge; Jim Bale; Michael Bamshad; Deborah Barbouth; Pinar Bayrak-Toydemir; Anita Beck; Alan H. Beggs; Edward Behrens; Gill Bejerano; Hugo J. Bellen; Jimmy Bennett; Jonathan A. Bernstein; Gerard T. Berry; Anna Bican; Stephanie Bivona; Elizabeth Blue; John Bohnsack; Devon Bonner; Nicholas Borja; Lorenzo Botto; Lauren C. Briere; Elizabeth A. Burke; Lindsay C. Burrage; Manish J. Butte; Peter Byers; William E. Byrd; John Carey; Thomas Cassini; Sirisak Chanprasert; Hsiao Tuan Chao; Ivan Chinn; Gary D. Clark; Terra R. Coakley; Laurel A. Cobban; Joy D. Cogan; Matthew Coggins; Sessions Cole; Heather A. Colley; Heidi Cope; Brian Corner; Rosario Corona; William J. Craigen; Andrew B. Crouse; Michael Cunningham; Hongzheng Dai; Surendra Dasari; Joie Davis; Jyoti G. Dayal; Margaret Delgado; Esteban C. Dell'Angelica; Katrina Dipple; Daniel Doherty; Naghmeh Dorrani; Argenia L. Doss; Emilie D. Douine; Precilla D'Souza; Dawn Earl; David J. Eckstein; Lisa T. Emrick; Christine M. Eng; Kimberly Ezell; Marni Falk; Elizabeth L. Fieg; Paul G. Fisher; Brent L. Fogel; Jiayu Fu; William A. Gahl; Ian Glass; Page C. Goddard; Rena A. Godfrey; Joanna M. Gonzalez; Andrea Gropman; Meghan C. Halley; Rizwan Hamid; Neil Hanchard; Kelly Hassey; Nichole Hayes; Frances High; Anne Hing; Fuki M. Hisama; Ingrid A. Holm; Jason Hom; Martha Horike-Pyne; Yan Huang; Alden Huang; Sarah Hutchison; Wendy Introne; Kosuke Izumi; Gail P. Jarvik; Jeffrey Jarvik; Suman Jayadev; Orpa Jean-Marie; Vaidehi Jobanputra; Emerald Kaitryn; Shamika Ketkar; Dana Kiley; Gonench Kilich; Shilpa N. Kobren; Isaac S. Kohane; Jennefer N. Kohler; Susan Korrick; Deborah Krakow; Donna M. Krasnewich; Elijah Kravets; Seema R. Lalani; Christina Lam; Brendan C. Lanpher; Ian R. Lanza; Kumarie Latchman; Kimberly LeBlanc; Brendan H. Lee; Richard A. Lewis; Pengfei Liu; Nicola Longo; Sandra K. Loo; Joseph Loscalzo; Richard L. Maas; Ellen F. Macnamara; Calum A. MacRae; Valerie V. Maduro; Audrey Stephannie C. Maghiro; Rachel Mahoney; May Christine V. Malicdan; Laura A. Mamounas; Teri A. Manolio; Rong Mao; Ronit Marom; Gabor Marth; Beth A. Martin; Martin G. Martin; Julian A. Martínez-Agosto; Shruti Marwaha; Allyn McConkie-Rosell; Alexa T. McCray; Elisabeth McGee; Matthew Might; Danny Miller; Ghayda Mirzaa; Eva Morava; Paolo Moretti; Marie Morimoto; John J. Mulvihill; Mariko Nakano-Okuno; Stanley F. Nelson; Serena Neumann; Shirley Nieves-Rodriguez; Donna Novacic; Devin Oglesbee; James P. Orengo; Laura Pace; Stephen Pak; J. Carl Pallais; Jeanette C. Papp; Neil H. Parker; LéShon Peart; Leoyklang Petcharet; John A. Phillips; Jennifer E. Posey; Lorraine Potocki; Barbara N. Pusey Swerdzewski; Aaron Quinlan; Deepak A. Rao; Anna Raper; Wendy Raskind; Adriana Rebelo; Genecee Renteria; Chloe M. Reuter; Lynette Rives; Amy K. Robertson; Lance H. Rodan; Jill A. Rosenfeld; Elizabeth Rosenthal; Francis Rossignol; Maura Ruzhnikov; Timothy Schedl; Jimann Shin; Lilianna Solnica-Krezel; Jennifer Wambach

doi:10.1002/acn3.51963

Recurrent ATP1A1 variant Gly903Arg causes developmental delay, intellectual disability, and autism

Undiagnosed Diseases Network, Maike F. Dohrn, Guney Bademci, Adriana P. Rebelo, Médéric Jeanne, Nicholas A. Borja, Danique Beijer, Matt C. Danzi, Stephanie A. Bivona, Paul Gueguen, Mohammad F. Zafeer, Mustafa Tekin, Stephan Züchner, Maria T. Acosta, David R. Adams, Ben Afzali, Aimee Allworth, Raquel L. Alvarez, Justin Alvey, Ashley AndrewsEuan A. Ashley, Carlos A. Bacino, Ashok Balasubramanyam, Dustin Baldridge, Jim Bale, Michael Bamshad, Deborah Barbouth, Pinar Bayrak-Toydemir, Anita Beck, Alan H. Beggs, Edward Behrens, Gill Bejerano, Hugo J. Bellen, Jimmy Bennett, Jonathan A. Bernstein, Gerard T. Berry, Anna Bican, Stephanie Bivona, Elizabeth Blue, John Bohnsack, Devon Bonner, Nicholas Borja, Lorenzo Botto, Lauren C. Briere, Elizabeth A. Burke, Lindsay C. Burrage, Manish J. Butte, Peter Byers, William E. Byrd, John Carey, Thomas Cassini, Sirisak Chanprasert, Hsiao Tuan Chao, Ivan Chinn, Gary D. Clark, Terra R. Coakley, Laurel A. Cobban, Joy D. Cogan, Matthew Coggins, Sessions Cole, Heather A. Colley, Heidi Cope, Brian Corner, Rosario Corona, William J. Craigen, Andrew B. Crouse, Michael Cunningham, Hongzheng Dai, Surendra Dasari, Joie Davis, Jyoti G. Dayal, Margaret Delgado, Esteban C. Dell'Angelica, Katrina Dipple, Daniel Doherty, Naghmeh Dorrani, Argenia L. Doss, Emilie D. Douine, Precilla D'Souza, Dawn Earl, David J. Eckstein, Lisa T. Emrick, Christine M. Eng, Kimberly Ezell, Marni Falk, Elizabeth L. Fieg, Paul G. Fisher, Brent L. Fogel, Jiayu Fu, William A. Gahl, Ian Glass, Page C. Goddard, Rena A. Godfrey, Joanna M. Gonzalez, Andrea Gropman, Meghan C. Halley, Rizwan Hamid, Neil Hanchard, Kelly Hassey, Nichole Hayes, Frances High, Anne Hing, Fuki M. Hisama, Ingrid A. Holm, Jason Hom, Martha Horike-Pyne, Yan Huang, Alden Huang, Sarah Hutchison, Wendy Introne, Kosuke Izumi, Gail P. Jarvik, Jeffrey Jarvik, Suman Jayadev, Orpa Jean-Marie, Vaidehi Jobanputra, Emerald Kaitryn, Shamika Ketkar, Dana Kiley, Gonench Kilich, Shilpa N. Kobren, Isaac S. Kohane, Jennefer N. Kohler, Susan Korrick, Deborah Krakow, Donna M. Krasnewich, Elijah Kravets, Seema R. Lalani, Christina Lam, Brendan C. Lanpher, Ian R. Lanza, Kumarie Latchman, Kimberly LeBlanc, Brendan H. Lee, Richard A. Lewis, Pengfei Liu, Nicola Longo, Sandra K. Loo, Joseph Loscalzo, Richard L. Maas, Ellen F. Macnamara, Calum A. MacRae, Valerie V. Maduro, Audrey Stephannie C. Maghiro, Rachel Mahoney, May Christine V. Malicdan, Laura A. Mamounas, Teri A. Manolio, Rong Mao, Ronit Marom, Gabor Marth, Beth A. Martin, Martin G. Martin, Julian A. Martínez-Agosto, Shruti Marwaha, Allyn McConkie-Rosell, Alexa T. McCray, Elisabeth McGee, Matthew Might, Danny Miller, Ghayda Mirzaa, Eva Morava, Paolo Moretti, Marie Morimoto, John J. Mulvihill, Mariko Nakano-Okuno, Stanley F. Nelson, Serena Neumann, Shirley Nieves-Rodriguez, Donna Novacic, Devin Oglesbee, James P. Orengo, Laura Pace, Stephen Pak, J. Carl Pallais, Jeanette C. Papp, Neil H. Parker, LéShon Peart, Leoyklang Petcharet, John A. Phillips, Jennifer E. Posey, Lorraine Potocki, Barbara N. Pusey Swerdzewski, Aaron Quinlan, Deepak A. Rao, Anna Raper, Wendy Raskind, Adriana Rebelo, Genecee Renteria, Chloe M. Reuter, Lynette Rives, Amy K. Robertson, Lance H. Rodan, Jill A. Rosenfeld, Elizabeth Rosenthal, Francis Rossignol, Maura Ruzhnikov, Timothy Schedl, Jimann Shin, Lilianna Solnica-Krezel, Jennifer Wambach

Research output: Contribution to journal › Article › peer-review

Abstract

ATP1A1 encodes a sodium-potassium ATPase that has been linked to several neurological diseases. Using exome and genome sequencing, we identified the heterozygous ATP1A1 variant NM_000701.8: c.2707G>A;p.(Gly903Arg) in two unrelated children presenting with delayed motor and speech development and autism. While absent in controls, the variant occurred de novo in one proband and co-segregated in two affected half-siblings, with mosaicism in the healthy mother. Using a specific ouabain resistance assay in mutant transfected HEK cells, we found significantly reduced cell viability. Demonstrating loss of ATPase function, we conclude that this novel variant is pathogenic, expanding the phenotype spectrum of ATP1A1.

Original language	English
Pages (from-to)	1075-1079
Number of pages	5
Journal	Annals of Clinical and Translational Neurology
Volume	11
Issue number	4
DOIs	https://doi.org/10.1002/acn3.51963
State	Published - Apr 2024

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10.1002/acn3.51963

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Undiagnosed Diseases Network, Dohrn, M. F., Bademci, G., Rebelo, A. P., Jeanne, M., Borja, N. A., Beijer, D., Danzi, M. C., Bivona, S. A., Gueguen, P., Zafeer, M. F., Tekin, M., Züchner, S., Acosta, M. T., Adams, D. R., Afzali, B., Allworth, A., Alvarez, R. L., Alvey, J., ... Wambach, J. (2024). Recurrent ATP1A1 variant Gly903Arg causes developmental delay, intellectual disability, and autism. Annals of Clinical and Translational Neurology, 11(4), 1075-1079. https://doi.org/10.1002/acn3.51963

@article{ae80d1fc4d2b4ae8a0991c800b275864,

title = "Recurrent ATP1A1 variant Gly903Arg causes developmental delay, intellectual disability, and autism",

abstract = "ATP1A1 encodes a sodium-potassium ATPase that has been linked to several neurological diseases. Using exome and genome sequencing, we identified the heterozygous ATP1A1 variant NM_000701.8: c.2707G>A;p.(Gly903Arg) in two unrelated children presenting with delayed motor and speech development and autism. While absent in controls, the variant occurred de novo in one proband and co-segregated in two affected half-siblings, with mosaicism in the healthy mother. Using a specific ouabain resistance assay in mutant transfected HEK cells, we found significantly reduced cell viability. Demonstrating loss of ATPase function, we conclude that this novel variant is pathogenic, expanding the phenotype spectrum of ATP1A1.",

author = "{Undiagnosed Diseases Network} and Dohrn, {Maike F.} and Guney Bademci and Rebelo, {Adriana P.} and M{\'e}d{\'e}ric Jeanne and Borja, {Nicholas A.} and Danique Beijer and Danzi, {Matt C.} and Bivona, {Stephanie A.} and Paul Gueguen and Zafeer, {Mohammad F.} and Mustafa Tekin and Stephan Z{\"u}chner and Acosta, {Maria T.} and Adams, {David R.} and Ben Afzali and Aimee Allworth and Alvarez, {Raquel L.} and Justin Alvey and Ashley Andrews and Ashley, {Euan A.} and Bacino, {Carlos A.} and Ashok Balasubramanyam and Dustin Baldridge and Jim Bale and Michael Bamshad and Deborah Barbouth and Pinar Bayrak-Toydemir and Anita Beck and Beggs, {Alan H.} and Edward Behrens and Gill Bejerano and Bellen, {Hugo J.} and Jimmy Bennett and Bernstein, {Jonathan A.} and Berry, {Gerard T.} and Anna Bican and Stephanie Bivona and Elizabeth Blue and John Bohnsack and Devon Bonner and Nicholas Borja and Lorenzo Botto and Briere, {Lauren C.} and Burke, {Elizabeth A.} and Burrage, {Lindsay C.} and Butte, {Manish J.} and Peter Byers and Byrd, {William E.} and John Carey and Thomas Cassini and Sirisak Chanprasert and Chao, {Hsiao Tuan} and Ivan Chinn and Clark, {Gary D.} and Coakley, {Terra R.} and Cobban, {Laurel A.} and Cogan, {Joy D.} and Matthew Coggins and Sessions Cole and Colley, {Heather A.} and Heidi Cope and Brian Corner and Rosario Corona and Craigen, {William J.} and Crouse, {Andrew B.} and Michael Cunningham and Hongzheng Dai and Surendra Dasari and Joie Davis and Dayal, {Jyoti G.} and Margaret Delgado and Dell'Angelica, {Esteban C.} and Katrina Dipple and Daniel Doherty and Naghmeh Dorrani and Doss, {Argenia L.} and Douine, {Emilie D.} and Precilla D'Souza and Dawn Earl and Eckstein, {David J.} and Emrick, {Lisa T.} and Eng, {Christine M.} and Kimberly Ezell and Marni Falk and Fieg, {Elizabeth L.} and Fisher, {Paul G.} and Fogel, {Brent L.} and Jiayu Fu and Gahl, {William A.} and Ian Glass and Goddard, {Page C.} and Godfrey, {Rena A.} and Gonzalez, {Joanna M.} and Andrea Gropman and Halley, {Meghan C.} and Rizwan Hamid and Neil Hanchard and Kelly Hassey and Nichole Hayes and Frances High and Anne Hing and Hisama, {Fuki M.} and Holm, {Ingrid A.} and Jason Hom and Martha Horike-Pyne and Yan Huang and Alden Huang and Sarah Hutchison and Wendy Introne and Kosuke Izumi and Jarvik, {Gail P.} and Jeffrey Jarvik and Suman Jayadev and Orpa Jean-Marie and Vaidehi Jobanputra and Emerald Kaitryn and Shamika Ketkar and Dana Kiley and Gonench Kilich and Kobren, {Shilpa N.} and Kohane, {Isaac S.} and Kohler, {Jennefer N.} and Susan Korrick and Deborah Krakow and Krasnewich, {Donna M.} and Elijah Kravets and Lalani, {Seema R.} and Christina Lam and Lanpher, {Brendan C.} and Lanza, {Ian R.} and Kumarie Latchman and Kimberly LeBlanc and Lee, {Brendan H.} and Lewis, {Richard A.} and Pengfei Liu and Nicola Longo and Loo, {Sandra K.} and Joseph Loscalzo and Maas, {Richard L.} and Macnamara, {Ellen F.} and MacRae, {Calum A.} and Maduro, {Valerie V.} and Maghiro, {Audrey Stephannie C.} and Rachel Mahoney and Malicdan, {May Christine V.} and Mamounas, {Laura A.} and Manolio, {Teri A.} and Rong Mao and Ronit Marom and Gabor Marth and Martin, {Beth A.} and Martin, {Martin G.} and Mart{\'i}nez-Agosto, {Julian A.} and Shruti Marwaha and Allyn McConkie-Rosell and McCray, {Alexa T.} and Elisabeth McGee and Matthew Might and Danny Miller and Ghayda Mirzaa and Eva Morava and Paolo Moretti and Marie Morimoto and Mulvihill, {John J.} and Mariko Nakano-Okuno and Nelson, {Stanley F.} and Serena Neumann and Shirley Nieves-Rodriguez and Donna Novacic and Devin Oglesbee and Orengo, {James P.} and Laura Pace and Stephen Pak and Pallais, {J. Carl} and Papp, {Jeanette C.} and Parker, {Neil H.} and L{\'e}Shon Peart and Leoyklang Petcharet and Phillips, {John A.} and Posey, {Jennifer E.} and Lorraine Potocki and {Pusey Swerdzewski}, {Barbara N.} and Aaron Quinlan and Rao, {Deepak A.} and Anna Raper and Wendy Raskind and Adriana Rebelo and Genecee Renteria and Reuter, {Chloe M.} and Lynette Rives and Robertson, {Amy K.} and Rodan, {Lance H.} and Rosenfeld, {Jill A.} and Elizabeth Rosenthal and Francis Rossignol and Maura Ruzhnikov and Timothy Schedl and Jimann Shin and Lilianna Solnica-Krezel and Jennifer Wambach",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.",

year = "2024",

month = apr,

doi = "10.1002/acn3.51963",

language = "English",

volume = "11",

pages = "1075--1079",

journal = "Annals of Clinical and Translational Neurology",

issn = "2328-9503",

number = "4",

}

Undiagnosed Diseases Network, Dohrn, MF, Bademci, G, Rebelo, AP, Jeanne, M, Borja, NA, Beijer, D, Danzi, MC, Bivona, SA, Gueguen, P, Zafeer, MF, Tekin, M, Züchner, S, Acosta, MT, Adams, DR, Afzali, B, Allworth, A, Alvarez, RL, Alvey, J, Andrews, A, Ashley, EA, Bacino, CA, Balasubramanyam, A, Baldridge, D, Bale, J, Bamshad, M, Barbouth, D, Bayrak-Toydemir, P, Beck, A, Beggs, AH, Behrens, E, Bejerano, G, Bellen, HJ, Bennett, J, Bernstein, JA, Berry, GT, Bican, A, Bivona, S, Blue, E, Bohnsack, J, Bonner, D, Borja, N, Botto, L, Briere, LC, Burke, EA, Burrage, LC, Butte, MJ, Byers, P, Byrd, WE, Carey, J, Cassini, T, Chanprasert, S, Chao, HT, Chinn, I, Clark, GD, Coakley, TR, Cobban, LA, Cogan, JD, Coggins, M, Cole, S, Colley, HA, Cope, H, Corner, B, Corona, R, Craigen, WJ, Crouse, AB, Cunningham, M, Dai, H, Dasari, S, Davis, J, Dayal, JG, Delgado, M, Dell'Angelica, EC, Dipple, K, Doherty, D, Dorrani, N, Doss, AL, Douine, ED, D'Souza, P, Earl, D, Eckstein, DJ, Emrick, LT, Eng, CM, Ezell, K, Falk, M, Fieg, EL, Fisher, PG, Fogel, BL, Fu, J, Gahl, WA, Glass, I, Goddard, PC, Godfrey, RA, Gonzalez, JM, Gropman, A, Halley, MC, Hamid, R, Hanchard, N, Hassey, K, Hayes, N, High, F, Hing, A, Hisama, FM, Holm, IA, Hom, J, Horike-Pyne, M, Huang, Y, Huang, A, Hutchison, S, Introne, W, Izumi, K, Jarvik, GP, Jarvik, J, Jayadev, S, Jean-Marie, O, Jobanputra, V, Kaitryn, E, Ketkar, S, Kiley, D, Kilich, G, Kobren, SN, Kohane, IS, Kohler, JN, Korrick, S, Krakow, D, Krasnewich, DM, Kravets, E, Lalani, SR, Lam, C, Lanpher, BC, Lanza, IR, Latchman, K, LeBlanc, K, Lee, BH, Lewis, RA, Liu, P, Longo, N, Loo, SK, Loscalzo, J, Maas, RL, Macnamara, EF, MacRae, CA, Maduro, VV, Maghiro, ASC, Mahoney, R, Malicdan, MCV, Mamounas, LA, Manolio, TA, Mao, R, Marom, R, Marth, G, Martin, BA, Martin, MG, Martínez-Agosto, JA, Marwaha, S, McConkie-Rosell, A, McCray, AT, McGee, E, Might, M, Miller, D, Mirzaa, G, Morava, E, Moretti, P, Morimoto, M, Mulvihill, JJ, Nakano-Okuno, M, Nelson, SF, Neumann, S, Nieves-Rodriguez, S, Novacic, D, Oglesbee, D, Orengo, JP, Pace, L, Pak, S, Pallais, JC, Papp, JC, Parker, NH, Peart, L, Petcharet, L, Phillips, JA, Posey, JE, Potocki, L, Pusey Swerdzewski, BN, Quinlan, A, Rao, DA, Raper, A, Raskind, W, Rebelo, A, Renteria, G, Reuter, CM, Rives, L, Robertson, AK, Rodan, LH, Rosenfeld, JA, Rosenthal, E, Rossignol, F, Ruzhnikov, M, Schedl, T , Shin, J , Solnica-Krezel, L & Wambach, J 2024, 'Recurrent ATP1A1 variant Gly903Arg causes developmental delay, intellectual disability, and autism', Annals of Clinical and Translational Neurology, vol. 11, no. 4, pp. 1075-1079. https://doi.org/10.1002/acn3.51963

TY - JOUR

T1 - Recurrent ATP1A1 variant Gly903Arg causes developmental delay, intellectual disability, and autism

AU - Undiagnosed Diseases Network

AU - Dohrn, Maike F.

AU - Bademci, Guney

AU - Rebelo, Adriana P.

AU - Jeanne, Médéric

AU - Borja, Nicholas A.

AU - Beijer, Danique

AU - Danzi, Matt C.

AU - Bivona, Stephanie A.

AU - Gueguen, Paul

AU - Zafeer, Mohammad F.

AU - Tekin, Mustafa

AU - Züchner, Stephan

AU - Acosta, Maria T.

AU - Adams, David R.

AU - Afzali, Ben

AU - Allworth, Aimee

AU - Alvarez, Raquel L.

AU - Alvey, Justin

AU - Andrews, Ashley

AU - Ashley, Euan A.

AU - Bacino, Carlos A.

AU - Balasubramanyam, Ashok

AU - Baldridge, Dustin

AU - Bale, Jim

AU - Bamshad, Michael

AU - Barbouth, Deborah

AU - Bayrak-Toydemir, Pinar

AU - Beck, Anita

AU - Beggs, Alan H.

AU - Behrens, Edward

AU - Bejerano, Gill

AU - Bellen, Hugo J.

AU - Bennett, Jimmy

AU - Bernstein, Jonathan A.

AU - Berry, Gerard T.

AU - Bican, Anna

AU - Bivona, Stephanie

AU - Blue, Elizabeth

AU - Bohnsack, John

AU - Bonner, Devon

AU - Borja, Nicholas

AU - Botto, Lorenzo

AU - Briere, Lauren C.

AU - Burke, Elizabeth A.

AU - Burrage, Lindsay C.

AU - Butte, Manish J.

AU - Byers, Peter

AU - Byrd, William E.

AU - Carey, John

AU - Cassini, Thomas

AU - Chanprasert, Sirisak

AU - Chao, Hsiao Tuan

AU - Chinn, Ivan

AU - Clark, Gary D.

AU - Coakley, Terra R.

AU - Cobban, Laurel A.

AU - Cogan, Joy D.

AU - Coggins, Matthew

AU - Cole, Sessions

AU - Colley, Heather A.

AU - Cope, Heidi

AU - Corner, Brian

AU - Corona, Rosario

AU - Craigen, William J.

AU - Crouse, Andrew B.

AU - Cunningham, Michael

AU - Dai, Hongzheng

AU - Dasari, Surendra

AU - Davis, Joie

AU - Dayal, Jyoti G.

AU - Delgado, Margaret

AU - Dell'Angelica, Esteban C.

AU - Dipple, Katrina

AU - Doherty, Daniel

AU - Dorrani, Naghmeh

AU - Doss, Argenia L.

AU - Douine, Emilie D.

AU - D'Souza, Precilla

AU - Earl, Dawn

AU - Eckstein, David J.

AU - Emrick, Lisa T.

AU - Eng, Christine M.

AU - Ezell, Kimberly

AU - Falk, Marni

AU - Fieg, Elizabeth L.

AU - Fisher, Paul G.

AU - Fogel, Brent L.

AU - Fu, Jiayu

AU - Gahl, William A.

AU - Glass, Ian

AU - Goddard, Page C.

AU - Godfrey, Rena A.

AU - Gonzalez, Joanna M.

AU - Gropman, Andrea

AU - Halley, Meghan C.

AU - Hamid, Rizwan

AU - Hanchard, Neil

AU - Hassey, Kelly

AU - Hayes, Nichole

AU - High, Frances

AU - Hing, Anne

AU - Hisama, Fuki M.

AU - Holm, Ingrid A.

AU - Hom, Jason

AU - Horike-Pyne, Martha

AU - Huang, Yan

AU - Huang, Alden

AU - Hutchison, Sarah

AU - Introne, Wendy

AU - Izumi, Kosuke

AU - Jarvik, Gail P.

AU - Jarvik, Jeffrey

AU - Jayadev, Suman

AU - Jean-Marie, Orpa

AU - Jobanputra, Vaidehi

AU - Kaitryn, Emerald

AU - Ketkar, Shamika

AU - Kiley, Dana

AU - Kilich, Gonench

AU - Kobren, Shilpa N.

AU - Kohane, Isaac S.

AU - Kohler, Jennefer N.

AU - Korrick, Susan

AU - Krakow, Deborah

AU - Krasnewich, Donna M.

AU - Kravets, Elijah

AU - Lalani, Seema R.

AU - Lam, Christina

AU - Lanpher, Brendan C.

AU - Lanza, Ian R.

AU - Latchman, Kumarie

AU - LeBlanc, Kimberly

AU - Lee, Brendan H.

AU - Lewis, Richard A.

AU - Liu, Pengfei

AU - Longo, Nicola

AU - Loo, Sandra K.

AU - Loscalzo, Joseph

AU - Maas, Richard L.

AU - Macnamara, Ellen F.

AU - MacRae, Calum A.

AU - Maduro, Valerie V.

AU - Maghiro, Audrey Stephannie C.

AU - Mahoney, Rachel

AU - Malicdan, May Christine V.

AU - Mamounas, Laura A.

AU - Manolio, Teri A.

AU - Mao, Rong

AU - Marom, Ronit

AU - Marth, Gabor

AU - Martin, Beth A.

AU - Martin, Martin G.

AU - Martínez-Agosto, Julian A.

AU - Marwaha, Shruti

AU - McConkie-Rosell, Allyn

AU - McCray, Alexa T.

AU - McGee, Elisabeth

AU - Might, Matthew

AU - Miller, Danny

AU - Mirzaa, Ghayda

AU - Morava, Eva

AU - Moretti, Paolo

AU - Morimoto, Marie

AU - Mulvihill, John J.

AU - Nakano-Okuno, Mariko

AU - Nelson, Stanley F.

AU - Neumann, Serena

AU - Nieves-Rodriguez, Shirley

AU - Novacic, Donna

AU - Oglesbee, Devin

AU - Orengo, James P.

AU - Pace, Laura

AU - Pak, Stephen

AU - Pallais, J. Carl

AU - Papp, Jeanette C.

AU - Parker, Neil H.

AU - Peart, LéShon

AU - Petcharet, Leoyklang

AU - Phillips, John A.

AU - Posey, Jennifer E.

AU - Potocki, Lorraine

AU - Pusey Swerdzewski, Barbara N.

AU - Quinlan, Aaron

AU - Rao, Deepak A.

AU - Raper, Anna

AU - Raskind, Wendy

AU - Rebelo, Adriana

AU - Renteria, Genecee

AU - Reuter, Chloe M.

AU - Rives, Lynette

AU - Robertson, Amy K.

AU - Rodan, Lance H.

AU - Rosenfeld, Jill A.

AU - Rosenthal, Elizabeth

AU - Rossignol, Francis

AU - Ruzhnikov, Maura

AU - Schedl, Timothy

AU - Shin, Jimann

AU - Solnica-Krezel, Lilianna

AU - Wambach, Jennifer

PY - 2024/4

Y1 - 2024/4

N2 - ATP1A1 encodes a sodium-potassium ATPase that has been linked to several neurological diseases. Using exome and genome sequencing, we identified the heterozygous ATP1A1 variant NM_000701.8: c.2707G>A;p.(Gly903Arg) in two unrelated children presenting with delayed motor and speech development and autism. While absent in controls, the variant occurred de novo in one proband and co-segregated in two affected half-siblings, with mosaicism in the healthy mother. Using a specific ouabain resistance assay in mutant transfected HEK cells, we found significantly reduced cell viability. Demonstrating loss of ATPase function, we conclude that this novel variant is pathogenic, expanding the phenotype spectrum of ATP1A1.

AB - ATP1A1 encodes a sodium-potassium ATPase that has been linked to several neurological diseases. Using exome and genome sequencing, we identified the heterozygous ATP1A1 variant NM_000701.8: c.2707G>A;p.(Gly903Arg) in two unrelated children presenting with delayed motor and speech development and autism. While absent in controls, the variant occurred de novo in one proband and co-segregated in two affected half-siblings, with mosaicism in the healthy mother. Using a specific ouabain resistance assay in mutant transfected HEK cells, we found significantly reduced cell viability. Demonstrating loss of ATPase function, we conclude that this novel variant is pathogenic, expanding the phenotype spectrum of ATP1A1.

UR - http://www.scopus.com/inward/record.url?scp=85188514386&partnerID=8YFLogxK

U2 - 10.1002/acn3.51963

DO - 10.1002/acn3.51963

M3 - Article

C2 - 38504481

AN - SCOPUS:85188514386

SN - 2328-9503

VL - 11

SP - 1075

EP - 1079

JO - Annals of Clinical and Translational Neurology

JF - Annals of Clinical and Translational Neurology

IS - 4

ER -

Recurrent ATP1A1 variant Gly903Arg causes developmental delay, intellectual disability, and autism

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