Exome and genome sequencing in a heterogeneous population of patients with rare disease: Identifying predictors of a diagnosis

Undiagnosed Diseases Network; Jenna Pucel; Lauren C. Briere; Chloe Reuter; Perman Gochyyev; Maria T. Acosta; David R. Adams; Raquel L. Alvarez; Justin Alvey; Aimee Allworth; Ashley Andrews; Euan A. Ashley; Carlos A. Bacino; Guney Bademci; 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; Lorenzo Botto; Gabrielle Brown; Elizabeth A. Burke; Lindsay C. Burrage; Manish J. Butte; Peter Byers; William E. Byrd; John Carey; Olveen Carrasquillo; Thomas Cassini; Ta Chen Peter Chang; Sirisak Chanprasert; Hsiao Tuan Chao; Ivan Chinn; Gary D. Clark; Terra R. Coakley; Laurel A. Cobban; Joy D. Cogan; Matthew Coggins; F. Sessions Cole; Heather A. Colley; Heidi Cope; Rosario Corona; William J. Craigen; Andrew B. Crouse; Michael Cunningham; Precilla D'Souza; Hongzheng Dai; Surendra Dasari; Joie Davis; Jyoti G. Dayal; Esteban C. Dell'Angelica; Katrina Dipple; Daniel Doherty; Naghmeh Dorrani; Argenia L. Doss; Emilie D. Douine; Dawn Earl; David J. Eckstein; Lisa T. Emrick; Christine M. Eng; Marni Falk; Elizabeth L. Fieg; Paul G. Fisher; Brent L. Fogel; Irman Forghani; William A. Gahl; Ian Glass; Bernadette Gochuico; Page C. Goddard; Rena A. Godfrey; Alana Grajewski; Don Hadley; Meghan C. Halley; Rizwan Hamid; Kelly Hassey; Nichole Hayes; Frances High; Anne Hing; Fuki M. Hisama; Ingrid A. Holm; Jason Hom; Martha Horike-Pyne; Alden Huang; Sarah Hutchison; Wendy Introne; Rosario Isasi; 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; Byron Lam; Christina Lam; Brendan C. Lanpher; Ian R. Lanza; Kimberly LeBlanc; Brendan H. Lee; Roy Levitt; Richard A. Lewis; Pengfei Liu; Xue Zhong Liu; Nicola Longo; Sandra K. Loo; Joseph Loscalzo; Richard L. Maas; Ellen F. Macnamara; Calum A. MacRae; Valerie V. Maduro; Audrey Stephannie 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; Jacob McCauley; Allyn McConkie-Rosell; Alexa T. McCray; Elisabeth McGee; Matthew Might; Danny Miller; Ghayda Mirzaa; Eva Morava; Paolo Moretti; John J. Mulvihill; Mariko Nakano-Okuno; Stanley F. Nelson; Shirley Nieves-Rodriguez; Donna Novacic; Devin Oglesbee; James P. Orengo; Laura Pace; Stephen Pak; J. Carl Pallais; Christina G.S. Palmer; Jeanette C. Papp; Neil H. Parker; John A. Phillips; Jennifer E. Posey; Lorraine Potocki; Barbara N. Pusey Swerdzewski; Aaron Quinlan; Deepak A. Rao; Anna Raper; Wendy Raskind; Genecee Renteria; Chloe M. Reuter; Lynette Rives; Amy K. Robertson; Lance H. Rodan; Jill A. Rosenfeld; Elizabeth Rosenthal; Francis Rossignol; Maura Ruzhnikov; Ralph Sacco; Jacinda B. Sampson; Mario Saporta; Judy Schaechter; Timothy Schedl; Kelly Schoch; Daryl A. Scott; Elaine Seto; Vandana Shashi; Emily Shelkowitz; Sam Sheppeard; Jimann Shin; Edwin K. Silverman; Lilianna Solnica-Krezel; Jennifer Wambach

doi:10.1016/j.gim.2024.101115

Exome and genome sequencing in a heterogeneous population of patients with rare disease: Identifying predictors of a diagnosis

Undiagnosed Diseases Network, Jenna Pucel, Lauren C. Briere, Chloe Reuter, Perman Gochyyev, Maria T. Acosta, David R. Adams, Raquel L. Alvarez, Justin Alvey, Aimee Allworth, Ashley Andrews, Euan A. Ashley, Carlos A. Bacino, Guney Bademci, Ashok Balasubramanyam, Dustin Baldridge, Jim Bale, Michael Bamshad, Deborah Barbouth, Pinar Bayrak-ToydemirAnita 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, Lorenzo Botto, Gabrielle Brown, Elizabeth A. Burke, Lindsay C. Burrage, Manish J. Butte, Peter Byers, William E. Byrd, John Carey, Olveen Carrasquillo, Thomas Cassini, Ta Chen Peter Chang, Sirisak Chanprasert, Hsiao Tuan Chao, Ivan Chinn, Gary D. Clark, Terra R. Coakley, Laurel A. Cobban, Joy D. Cogan, Matthew Coggins, F. Sessions Cole, Heather A. Colley, Heidi Cope, Rosario Corona, William J. Craigen, Andrew B. Crouse, Michael Cunningham, Precilla D'Souza, Hongzheng Dai, Surendra Dasari, Joie Davis, Jyoti G. Dayal, Esteban C. Dell'Angelica, Katrina Dipple, Daniel Doherty, Naghmeh Dorrani, Argenia L. Doss, Emilie D. Douine, Dawn Earl, David J. Eckstein, Lisa T. Emrick, Christine M. Eng, Marni Falk, Elizabeth L. Fieg, Paul G. Fisher, Brent L. Fogel, Irman Forghani, William A. Gahl, Ian Glass, Bernadette Gochuico, Page C. Goddard, Rena A. Godfrey, Alana Grajewski, Don Hadley, Meghan C. Halley, Rizwan Hamid, Kelly Hassey, Nichole Hayes, Frances High, Anne Hing, Fuki M. Hisama, Ingrid A. Holm, Jason Hom, Martha Horike-Pyne, Alden Huang, Sarah Hutchison, Wendy Introne, Rosario Isasi, 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, Byron Lam, Christina Lam, Brendan C. Lanpher, Ian R. Lanza, Kimberly LeBlanc, Brendan H. Lee, Roy Levitt, Richard A. Lewis, Pengfei Liu, Xue Zhong Liu, Nicola Longo, Sandra K. Loo, Joseph Loscalzo, Richard L. Maas, Ellen F. Macnamara, Calum A. MacRae, Valerie V. Maduro, Audrey Stephannie 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, Jacob McCauley, Allyn McConkie-Rosell, Alexa T. McCray, Elisabeth McGee, Matthew Might, Danny Miller, Ghayda Mirzaa, Eva Morava, Paolo Moretti, John J. Mulvihill, Mariko Nakano-Okuno, Stanley F. Nelson, Shirley Nieves-Rodriguez, Donna Novacic, Devin Oglesbee, James P. Orengo, Laura Pace, Stephen Pak, J. Carl Pallais, Christina G.S. Palmer, Jeanette C. Papp, Neil H. Parker, John A. Phillips, Jennifer E. Posey, Lorraine Potocki, Barbara N. Pusey Swerdzewski, Aaron Quinlan, Deepak A. Rao, Anna Raper, Wendy Raskind, Genecee Renteria, Chloe M. Reuter, Lynette Rives, Amy K. Robertson, Lance H. Rodan, Jill A. Rosenfeld, Elizabeth Rosenthal, Francis Rossignol, Maura Ruzhnikov, Ralph Sacco, Jacinda B. Sampson, Mario Saporta, Judy Schaechter, Timothy Schedl, Kelly Schoch, Daryl A. Scott, Elaine Seto, Vandana Shashi, Emily Shelkowitz, Sam Sheppeard, Jimann Shin, Edwin K. Silverman, Lilianna Solnica-Krezel, Jennifer Wambach

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

Abstract

Purpose: Exome (ES) and genome sequencing (GS) are increasingly being utilized for individuals with rare and undiagnosed diseases; however, guidelines on their use remain limited. This study aimed to identify factors associated with diagnosis by ES and/or GS in a heterogeneous population of patients with rare and undiagnosed diseases. Methods: In this case control study, we reviewed data from 400 diagnosed and 400 undiagnosed randomly selected participants in the Undiagnosed Diseases Network, all of whom had undergone ES and/or GS. We analyzed factors associated with receiving a diagnosis by ES and/or GS. Results: Factors associated with a decreased odds of being diagnosed included adult symptom onset, singleton sequencing, and having undergone ES and/or GS before acceptance to the Undiagnosed Diseases Network (48%, 51%, and 32% lower odds, respectively). Factors that increased the odds of being diagnosed by ES and/or GS included having primarily neurological symptoms and having undergone prior chromosomal microarray testing (44% and 59% higher odds, respectively). Conclusion: We identified several factors that were associated with receiving a diagnosis by ES and/or GS. This will ideally inform the utilization of ES and/or GS and help manage expectations of individuals and families undergoing these tests.

Original language	English
Article number	101115
Journal	Genetics in Medicine
Volume	26
Issue number	6
DOIs	https://doi.org/10.1016/j.gim.2024.101115
State	Published - Jun 2024

Keywords

Exome sequencing
Genome sequencing
Predictors of a diagnosis
Rare disease
Undiagnosed disease

Access to Document

10.1016/j.gim.2024.101115

Cite this

Undiagnosed Diseases Network, Pucel, J., Briere, L. C., Reuter, C., Gochyyev, P., Acosta, M. T., Adams, D. R., Alvarez, R. L., Alvey, J., Allworth, A., Andrews, A., Ashley, E. A., Bacino, C. A., Bademci, G., Balasubramanyam, A., Baldridge, D., Bale, J., Bamshad, M., Barbouth, D., ... Wambach, J. (2024). Exome and genome sequencing in a heterogeneous population of patients with rare disease: Identifying predictors of a diagnosis. Genetics in Medicine, 26(6), Article 101115. https://doi.org/10.1016/j.gim.2024.101115

@article{f1ebfc5aadb54c15a4a1f14805bc196d,

title = "Exome and genome sequencing in a heterogeneous population of patients with rare disease: Identifying predictors of a diagnosis",

abstract = "Purpose: Exome (ES) and genome sequencing (GS) are increasingly being utilized for individuals with rare and undiagnosed diseases; however, guidelines on their use remain limited. This study aimed to identify factors associated with diagnosis by ES and/or GS in a heterogeneous population of patients with rare and undiagnosed diseases. Methods: In this case control study, we reviewed data from 400 diagnosed and 400 undiagnosed randomly selected participants in the Undiagnosed Diseases Network, all of whom had undergone ES and/or GS. We analyzed factors associated with receiving a diagnosis by ES and/or GS. Results: Factors associated with a decreased odds of being diagnosed included adult symptom onset, singleton sequencing, and having undergone ES and/or GS before acceptance to the Undiagnosed Diseases Network (48%, 51%, and 32% lower odds, respectively). Factors that increased the odds of being diagnosed by ES and/or GS included having primarily neurological symptoms and having undergone prior chromosomal microarray testing (44% and 59% higher odds, respectively). Conclusion: We identified several factors that were associated with receiving a diagnosis by ES and/or GS. This will ideally inform the utilization of ES and/or GS and help manage expectations of individuals and families undergoing these tests.",

keywords = "Exome sequencing, Genome sequencing, Predictors of a diagnosis, Rare disease, Undiagnosed disease",

author = "{Undiagnosed Diseases Network} and Jenna Pucel and Briere, {Lauren C.} and Chloe Reuter and Perman Gochyyev and Acosta, {Maria T.} and Adams, {David R.} and Alvarez, {Raquel L.} and Justin Alvey and Aimee Allworth and Ashley Andrews and Ashley, {Euan A.} and Bacino, {Carlos A.} and Guney Bademci 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 Lorenzo Botto and Gabrielle Brown and Burke, {Elizabeth A.} and Burrage, {Lindsay C.} and Butte, {Manish J.} and Peter Byers and Byrd, {William E.} and John Carey and Olveen Carrasquillo and Thomas Cassini and {Peter Chang}, {Ta Chen} 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 Cole, {F. Sessions} and Colley, {Heather A.} and Heidi Cope and Rosario Corona and Craigen, {William J.} and Crouse, {Andrew B.} and Michael Cunningham and Precilla D'Souza and Hongzheng Dai and Surendra Dasari and Joie Davis and Dayal, {Jyoti G.} and Dell'Angelica, {Esteban C.} and Katrina Dipple and Daniel Doherty and Naghmeh Dorrani and Doss, {Argenia L.} and Douine, {Emilie D.} and Dawn Earl and Eckstein, {David J.} and Emrick, {Lisa T.} and Eng, {Christine M.} and Marni Falk and Fieg, {Elizabeth L.} and Fisher, {Paul G.} and Fogel, {Brent L.} and Irman Forghani and Gahl, {William A.} and Ian Glass and Bernadette Gochuico and Goddard, {Page C.} and Godfrey, {Rena A.} and Alana Grajewski and Don Hadley and Halley, {Meghan C.} and Rizwan Hamid 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 Alden Huang and Sarah Hutchison and Wendy Introne and Rosario Isasi 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 Byron Lam and Christina Lam and Lanpher, {Brendan C.} and Lanza, {Ian R.} and Kimberly LeBlanc and Lee, {Brendan H.} and Roy Levitt and Lewis, {Richard A.} and Pengfei Liu and Liu, {Xue Zhong} 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} 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 Jacob McCauley 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 Mulvihill, {John J.} and Mariko Nakano-Okuno and Nelson, {Stanley F.} 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 Palmer, {Christina G.S.} and Papp, {Jeanette C.} and Parker, {Neil H.} 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 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 Ralph Sacco and Sampson, {Jacinda B.} and Mario Saporta and Judy Schaechter and Timothy Schedl and Kelly Schoch and Scott, {Daryl A.} and Elaine Seto and Vandana Shashi and Emily Shelkowitz and Sam Sheppeard and Jimann Shin and Silverman, {Edwin K.} and Lilianna Solnica-Krezel and Jennifer Wambach",

note = "Publisher Copyright: {\textcopyright} 2024 American College of Medical Genetics and Genomics",

year = "2024",

month = jun,

doi = "10.1016/j.gim.2024.101115",

language = "English",

volume = "26",

journal = "Genetics in Medicine",

issn = "1098-3600",

number = "6",

}

Undiagnosed Diseases Network, Pucel, J, Briere, LC, Reuter, C, Gochyyev, P, Acosta, MT, Adams, DR, Alvarez, RL, Alvey, J, Allworth, A, Andrews, A, Ashley, EA, Bacino, CA, Bademci, G, 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, Botto, L, Brown, G, Burke, EA, Burrage, LC, Butte, MJ, Byers, P, Byrd, WE, Carey, J, Carrasquillo, O, Cassini, T, Peter Chang, TC, Chanprasert, S, Chao, HT, Chinn, I, Clark, GD, Coakley, TR, Cobban, LA, Cogan, JD, Coggins, M, Cole, FS, Colley, HA, Cope, H, Corona, R, Craigen, WJ, Crouse, AB, Cunningham, M, D'Souza, P, Dai, H, Dasari, S, Davis, J, Dayal, JG, Dell'Angelica, EC, Dipple, K, Doherty, D, Dorrani, N, Doss, AL, Douine, ED, Earl, D, Eckstein, DJ, Emrick, LT, Eng, CM, Falk, M, Fieg, EL, Fisher, PG, Fogel, BL, Forghani, I, Gahl, WA, Glass, I, Gochuico, B, Goddard, PC, Godfrey, RA, Grajewski, A, Hadley, D, Halley, MC, Hamid, R, Hassey, K, Hayes, N, High, F, Hing, A, Hisama, FM, Holm, IA, Hom, J, Horike-Pyne, M, Huang, A, Hutchison, S, Introne, W, Isasi, R, 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, B, Lam, C, Lanpher, BC, Lanza, IR, LeBlanc, K, Lee, BH, Levitt, R, Lewis, RA, Liu, P, Liu, XZ, Longo, N, Loo, SK, Loscalzo, J, Maas, RL, Macnamara, EF, MacRae, CA, Maduro, VV, Maghiro, AS, Mahoney, R, Malicdan, MCV, Mamounas, LA, Manolio, TA, Mao, R, Marom, R, Marth, G, Martin, BA, Martin, MG, Martínez-Agosto, JA, Marwaha, S, McCauley, J, McConkie-Rosell, A, McCray, AT, McGee, E, Might, M, Miller, D, Mirzaa, G, Morava, E, Moretti, P, Mulvihill, JJ, Nakano-Okuno, M, Nelson, SF, Nieves-Rodriguez, S, Novacic, D, Oglesbee, D, Orengo, JP, Pace, L, Pak, S, Pallais, JC, Palmer, CGS, Papp, JC, Parker, NH, Phillips, JA, Posey, JE, Potocki, L, Pusey Swerdzewski, BN, Quinlan, A, Rao, DA, Raper, A, Raskind, W, Renteria, G, Reuter, CM, Rives, L, Robertson, AK, Rodan, LH, Rosenfeld, JA, Rosenthal, E, Rossignol, F, Ruzhnikov, M, Sacco, R, Sampson, JB, Saporta, M, Schaechter, J, Schedl, T, Schoch, K, Scott, DA, Seto, E, Shashi, V, Shelkowitz, E, Sheppeard, S, Shin, J, Silverman, EK, Solnica-Krezel, L & Wambach, J 2024, 'Exome and genome sequencing in a heterogeneous population of patients with rare disease: Identifying predictors of a diagnosis', Genetics in Medicine, vol. 26, no. 6, 101115. https://doi.org/10.1016/j.gim.2024.101115

TY - JOUR

T1 - Exome and genome sequencing in a heterogeneous population of patients with rare disease

T2 - Identifying predictors of a diagnosis

AU - Undiagnosed Diseases Network

AU - Pucel, Jenna

AU - Briere, Lauren C.

AU - Reuter, Chloe

AU - Gochyyev, Perman

AU - Acosta, Maria T.

AU - Adams, David R.

AU - Alvarez, Raquel L.

AU - Alvey, Justin

AU - Allworth, Aimee

AU - Andrews, Ashley

AU - Ashley, Euan A.

AU - Bacino, Carlos A.

AU - Bademci, Guney

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 - Botto, Lorenzo

AU - Brown, Gabrielle

AU - Burke, Elizabeth A.

AU - Burrage, Lindsay C.

AU - Butte, Manish J.

AU - Byers, Peter

AU - Byrd, William E.

AU - Carey, John

AU - Carrasquillo, Olveen

AU - Cassini, Thomas

AU - Peter Chang, Ta Chen

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, F. Sessions

AU - Colley, Heather A.

AU - Cope, Heidi

AU - Corona, Rosario

AU - Craigen, William J.

AU - Crouse, Andrew B.

AU - Cunningham, Michael

AU - D'Souza, Precilla

AU - Dai, Hongzheng

AU - Dasari, Surendra

AU - Davis, Joie

AU - Dayal, Jyoti G.

AU - Dell'Angelica, Esteban C.

AU - Dipple, Katrina

AU - Doherty, Daniel

AU - Dorrani, Naghmeh

AU - Doss, Argenia L.

AU - Douine, Emilie D.

AU - Earl, Dawn

AU - Eckstein, David J.

AU - Emrick, Lisa T.

AU - Eng, Christine M.

AU - Falk, Marni

AU - Fieg, Elizabeth L.

AU - Fisher, Paul G.

AU - Fogel, Brent L.

AU - Forghani, Irman

AU - Gahl, William A.

AU - Glass, Ian

AU - Gochuico, Bernadette

AU - Goddard, Page C.

AU - Godfrey, Rena A.

AU - Grajewski, Alana

AU - Hadley, Don

AU - Halley, Meghan C.

AU - Hamid, Rizwan

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, Alden

AU - Hutchison, Sarah

AU - Introne, Wendy

AU - Isasi, Rosario

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, Byron

AU - Lam, Christina

AU - Lanpher, Brendan C.

AU - Lanza, Ian R.

AU - LeBlanc, Kimberly

AU - Lee, Brendan H.

AU - Levitt, Roy

AU - Lewis, Richard A.

AU - Liu, Pengfei

AU - Liu, Xue Zhong

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

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 - McCauley, Jacob

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 - Mulvihill, John J.

AU - Nakano-Okuno, Mariko

AU - Nelson, Stanley F.

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 - Palmer, Christina G.S.

AU - Papp, Jeanette C.

AU - Parker, Neil H.

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 - 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 - Sacco, Ralph

AU - Sampson, Jacinda B.

AU - Saporta, Mario

AU - Schaechter, Judy

AU - Schedl, Timothy

AU - Schoch, Kelly

AU - Scott, Daryl A.

AU - Seto, Elaine

AU - Shashi, Vandana

AU - Shelkowitz, Emily

AU - Sheppeard, Sam

AU - Shin, Jimann

AU - Silverman, Edwin K.

AU - Solnica-Krezel, Lilianna

AU - Wambach, Jennifer

PY - 2024/6

Y1 - 2024/6

N2 - Purpose: Exome (ES) and genome sequencing (GS) are increasingly being utilized for individuals with rare and undiagnosed diseases; however, guidelines on their use remain limited. This study aimed to identify factors associated with diagnosis by ES and/or GS in a heterogeneous population of patients with rare and undiagnosed diseases. Methods: In this case control study, we reviewed data from 400 diagnosed and 400 undiagnosed randomly selected participants in the Undiagnosed Diseases Network, all of whom had undergone ES and/or GS. We analyzed factors associated with receiving a diagnosis by ES and/or GS. Results: Factors associated with a decreased odds of being diagnosed included adult symptom onset, singleton sequencing, and having undergone ES and/or GS before acceptance to the Undiagnosed Diseases Network (48%, 51%, and 32% lower odds, respectively). Factors that increased the odds of being diagnosed by ES and/or GS included having primarily neurological symptoms and having undergone prior chromosomal microarray testing (44% and 59% higher odds, respectively). Conclusion: We identified several factors that were associated with receiving a diagnosis by ES and/or GS. This will ideally inform the utilization of ES and/or GS and help manage expectations of individuals and families undergoing these tests.

AB - Purpose: Exome (ES) and genome sequencing (GS) are increasingly being utilized for individuals with rare and undiagnosed diseases; however, guidelines on their use remain limited. This study aimed to identify factors associated with diagnosis by ES and/or GS in a heterogeneous population of patients with rare and undiagnosed diseases. Methods: In this case control study, we reviewed data from 400 diagnosed and 400 undiagnosed randomly selected participants in the Undiagnosed Diseases Network, all of whom had undergone ES and/or GS. We analyzed factors associated with receiving a diagnosis by ES and/or GS. Results: Factors associated with a decreased odds of being diagnosed included adult symptom onset, singleton sequencing, and having undergone ES and/or GS before acceptance to the Undiagnosed Diseases Network (48%, 51%, and 32% lower odds, respectively). Factors that increased the odds of being diagnosed by ES and/or GS included having primarily neurological symptoms and having undergone prior chromosomal microarray testing (44% and 59% higher odds, respectively). Conclusion: We identified several factors that were associated with receiving a diagnosis by ES and/or GS. This will ideally inform the utilization of ES and/or GS and help manage expectations of individuals and families undergoing these tests.

KW - Exome sequencing

KW - Genome sequencing

KW - Predictors of a diagnosis

KW - Rare disease

KW - Undiagnosed disease

UR - http://www.scopus.com/inward/record.url?scp=85190603934&partnerID=8YFLogxK

U2 - 10.1016/j.gim.2024.101115

DO - 10.1016/j.gim.2024.101115

M3 - Article

C2 - 38436216

AN - SCOPUS:85190603934

SN - 1098-3600

VL - 26

JO - Genetics in Medicine

JF - Genetics in Medicine

IS - 6

M1 - 101115

ER -

Exome and genome sequencing in a heterogeneous population of patients with rare disease: Identifying predictors of a diagnosis

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