The impact of clinical genome sequencing in a global population with suspected rare genetic disease

被引：7

作者：

Thorpe, Erin ^{[1
,40
]}

Williams, Taylor ^{[2
]}

Shaw, Chad ^{[2
,3
,4
]}

Chekalin, Evgenii ^{[1
]}

Ortega, Julia ^{[1
,5
]}

Robinson, Keisha ^{[1
]}

Button, Jason ^{[1
]}

Jones, Marilyn C. ^{[6
,7
]}

del Campo, Miguel ^{[6
,7
]}

Basel, Donald ^{[8
]}

McCarrier, Julie ^{[8
]}

Keppen, Laura Davis ^{[9
]}

Royer, Erin ^{[10
]}

Foster-Bonds, Romina ^{[11
]}

Duenas-Roque, Milagros M. ^{[12
]}

Urraca, Nora ^{[13
]}

Bosfield, Kerri ^{[13
]}

Brown, Chester W. ^{[13
]}

Lydigsen, Holly ^{[13
]}

Mroczkowski, Henry J. ^{[13
]}

Ward, Jewell ^{[13
]}

Sirchia, Fabio ^{[14
,15
]}

Giorgio, Elisa ^{[14
,16
]}

Vaux, Keith ^{[17
]}

Salguero, Hildegard Pena ^{[18
]}

Lumaka, Aime ^{[19
,20
]}

Mubungu, Gerrye ^{[19
]}

Makay, Prince ^{[19
]}

Ngole, Mamy ^{[19
]}

Lukusa, Prosper Tshilobo ^{[19
]}

Vanderver, Adeline ^{[21
,22
]}

Muirhead, Kayla ^{[23
]}

Sherbini, Omar ^{[21
]}

Lah, Melissa D. ^{[24
]}

Anderson, Katelynn ^{[24
]}

Bazalar-Montoya, Jeny ^{[25
]}

Rodriguez, Richard S. ^{[25
]}

Cornejo-Olivas, Mario ^{[26
,27
]}

Milla-Neyra, Karina ^{[26
]}

Shinawi, Marwan ^{[28
,29
]}

Magoulas, Pilar ^{[30
]}

Henry, Duncan ^{[31
]}

Gibson, Kate ^{[32
]}

Wiafe, Samuel ^{[33
]}

Jayakar, Parul ^{[34
]}

Salyakina, Daria ^{[34
]}

Masser-Frye, Diane ^{[6
,35
]}

Serize, Arturo ^{[36
]}

Perez, Jorge E. ^{[36
]}

Taylor, Alan ^{[37
]}

机构：

[1] Illumina Inc, San Diego, CA 92122 USA

[2] Genet & Genom Serv PBC, Houston, TX USA

[3] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX USA

[4] Rice Univ, Dept Stat, Houston, TX USA

[5] C2N Diagnost, St Louis, MO USA

[6] Rady Childrens Hosp, San Diego, CA USA

[7] Univ Calif San Diego, San Diego, CA USA

[8] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI USA

[9] Sanford USD Med Ctr, Sioux Falls, SD USA

[10] USD Sanford Sch Med, Sanford Childrens Specialty Clin, Sanford Hlth, Sioux Falls, SD USA

[11] Rare Genom Inst, Los Angeles, CA USA

[12] Hosp Edgardo Rebagliati Martins EsSalud, Serv Genet, Lima, Peru

[13] Univ Tennessee, Bonheur Childrens Hosp, Hlth Sci Ctr, Memphis, TN USA

[14] Univ Pavia, Dept Mol Med, Pavia, Italy

[15] IRCCS San Matteo Fdn, Med Genet Unit, Pavia, Italy

[16] IRCCS Mondino Fdn, Med Genet Unit, Pavia, Italy

[17] Point Loma Pediat, San Diego, CA USA

[18] Padrino Childrens Fdn, Todos Santos, BCS, Mexico

[19] Univ Kinshasa, Ctr Genet Humaine, Kinshasa, DEM REP CONGO

[20] Ctr Human Genet, CHU, Liege, Belgium

[21] Childrens Hosp Philadelphia, Dept Pediat, Div Neurol, Philadelphia, PA USA

[22] Univ Penn, Perelman Sch Med, Dept Neurol, Philadelphia, PA USA

[23] Ambry Genet, Aliso Viejo, CA USA

[24] Indiana Univ Sch Med, Indianapolis, IN USA

[25] Inst Nacl Salud Nino San Borja, Lima, Peru

[26] Inst Nacl Ciencias Neurol, Neurogenet Res Ctr, Lima, Peru

[27] Univ Cient Sur, Neurogenet Working Grp, Lima, Peru

[28] Washington Univ, St Louis, MO USA

[29] St Louis Childrens Hosp, St Louis, MO USA

[30] Texas Childrens Hosp, Houston, TX USA

[31] UCSF Benioff Childrens Hosp, San Francisco, CA USA

[32] Canterbury Dist Hlth Board, Canterbury, New Zealand

[33] Rare Dis Ghana Initiat, Accra, Ghana

[34] Nicklaus Childrens Hlth Syst, Miami, FL USA

[35] San Diego Imperial Cty Dev Serv Inc, San Diego, CA USA

[36] South Miami Hosp, South Miami, FL USA

[37] Al Jalila Childrens Specialty Hosp, Al Jalila Genom Ctr Excellence, Dubai, U Arab Emirates

[38] Mohammed Bin Rashid Univ Med & Hlth Sci, Ctr Genom Discovery, Dubai, U Arab Emirates

[39] Veracyte, San Diego, CA USA

[40] Genet Alliance, Damascus, MD 20872 USA

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2024年 / 111卷 / 07期

关键词：

RECOMMENDATIONS; EXOME;

D O I：

10.1016/j.ajhg.2024.05.006

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

There is mounting evidence of the value of clinical genome sequencing (cGS) in individuals with suspected rare genetic disease (RGD), but cGS performance and impact on clinical care in a diverse population drawn from both high-income countries (HICs) and low- and middle-income countries (LMICs) has not been investigated. The iHope program, a philanthropic cGS initiative, established a network of 24 clinical sites in eight countries through which it provided cGS to individuals with signs or symptoms of an RGD and constrained access to molecular testing. A total of 1,004 individuals (median age, 6.5 years; 53.5% male) with diverse ancestral backgrounds (51.8% non-majority European) were assessed from June 2016 to September 2021. The diagnostic yield of cGS was 41.4% (416/1,004), with individuals from LMIC sites 1.7 times more likely to receive a positive test result compared to HIC sites (LMIC 56.5% [195/345] vs. HIC 33.5% [221/659], OR 2.6, 95% CI 1.9-3.4, p < 0.0001). A change in diagnostic evaluation occurred in 76.9% (514/668) of individuals. Change of management, inclusive of specialty referrals, imaging and testing, therapeutic interventions, and palliative care, was reported in 41.4% (285/694) of individuals, which increased to 69.2% (480/694) when genetic counseling and avoidance of additional testing were also included. Individuals from LMIC sites were as likely as their HIC counterparts to experience a change in diagnostic evaluation (OR 6.1, 95% CI 1.1-infinity, p = 0.05) and change of management (OR 0.9, 95% CI 0.5-1.3, p = 0.49). Increased access to genomic testing may support diagnostic equity and the reduction of global health care disparities.

引用

页码：1271 / 1281

页数：12

共 24 条

[1] Fast model-based estimation of ancestry in unrelated individuals [J].

Alexander, David H. ;

Novembre, John ;

Lange, Kenneth .

GENOME RESEARCH, 2009, 19 (09) :1655-1664

[2] A global reference for human genetic variation [J].

Altshuler, David M. ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Donnelly, Peter ;

Eichler, Evan E. ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Green, Eric D. ;

Hurles, Matthew E. ;

Knoppers, Bartha M. ;

Korbel, Jan O. ;

Lander, Eric S. ;

Lee, Charles ;

Lehrach, Hans ;

Mardis, Elaine R. ;

Marth, Gabor T. ;

McVean, Gil A. ;

Nickerson, Deborah A. ;

Wang, Jun ;

Wilson, Richard K. ;

Boerwinkle, Eric ;

Doddapaneni, Harsha ;

Han, Yi ;

Korchina, Viktoriya ;

Kovar, Christie ;

Lee, Sandra ;

Muzny, Donna ;

Reid, Jeffrey G. ;

Zhu, Yiming ;

Chang, Yuqi ;

Feng, Qiang ;

Fang, Xiaodong ;

Guo, Xiaosen ;

Jian, Min ;

Jiang, Hui ;

Jin, Xin ;

Lan, Tianming ;

Li, Guoqing ;

Li, Jingxiang ;

Li, Yingrui ;

Liu, Shengmao ;

Liu, Xiao ;

Lu, Yao ;

Ma, Xuedi ;

Tang, Meifang ;

Wang, Bo .

NATURE, 2015, 526 (7571) :68-+

[3] Successful application of genome sequencing in a diagnostic setting: 1007 index cases from a clinically heterogeneous cohort [J].

Bertoli-Avella, Aida M. ;

Beetz, Christian ;

Ameziane, Najim ;

Rocha, Maria Eugenia ;

Guatibonza, Pilar ;

Pereira, Catarina ;

Calvo, Maria ;

Herrera-Ordonez, Natalia ;

Segura-Castel, Monica ;

Diego-Alvarez, Dan ;

Zawada, Michal ;

Kandaswamy, Krishna K. ;

Werber, Martin ;

Paknia, Omid ;

Zielske, Susan ;

Ugrinovski, Dimitar ;

Warnack, Gitte ;

Kampe, Kapil ;

Iurascu, Marius-Ionut ;

Cozma, Claudia ;

Vogel, Florian ;

Alhashem, Amal ;

Hertecant, Jozef ;

Al-Shamsi, Aisha M. ;

Alswaid, Abdulrahman Faiz ;

Eyaid, Wafaa ;

Al Mutairi, Fuad ;

Alfares, Ahmed ;

Albalwi, Mohammed A. ;

Alfadhel, Majid ;

Al-Sannaa, Nouriya Abbas ;

Reardon, Willie ;

Alanay, Yasemin ;

Rolfs, Arndt ;

Bauer, Peter .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2021, 29 (01) :141-153

[4] Case for genome sequencing in infants and children with rare, undiagnosed or genetic diseases [J].

Bick, David ;

Jones, Marilyn ;

Taylor, Stacie L. ;

Taft, Ryan J. ;

Belmont, John .

JOURNAL OF MEDICAL GENETICS, 2019, 56 (12) :783-791

[5] Meta-analysis of the diagnostic and clinical utility of exome and genome sequencing in pediatric and adult patients with rare diseases across diverse populations [J].

Chung, Claudia C. Y. ;

Hue, Shirley P. Y. ;

Ng, Nicole Y. T. ;

Doong, Phoenix H. L. ;

Chu, Annie T. W. ;

Chung, Brian H. Y. .

GENETICS IN MEDICINE, 2023, 25 (09)

[6] Meta-analysis of the diagnostic and clinical utility of genome and exome sequencing and chromosomal microarray in children with suspected genetic diseases [J].

Clark, Michelle M. ;

Starke, Zornitza ;

Farnaes, Lauge ;

Tan, Tiong Y. ;

White, Susan M. ;

Dimmock, David ;

Kingsmore, Stephen F. .

NPJ GENOMIC MEDICINE, 2018, 3

[7]

Dicken J., 2021, RARE DIS LTD AVAILAB

[8] The genomic landscape of rare disorders in the Middle East [J].

El Naofal, Maha ;

Ramaswamy, Sathishkumar ;

Alsarhan, Ali ;

Nugud, Ahmed ;

Sarfraz, Fatima ;

Janbaz, Hiba ;

Taylor, Alan ;

Jain, Ruchi ;

Halabi, Nour ;

Yaslam, Sawsan ;

Alfalasi, Roudha ;

Shenbagam, Shruti ;

Rabea, Fatma ;

Bitzan, Martin ;

Yavuz, Lemis ;

Wafadari, Deena ;

Abulhoul, Hamda ;

Shankar, Shiva ;

Al Maazmi, Munira ;

Rizk, Ruba ;

Alloub, Zeinab ;

Elbashir, Haitham ;

Babiker, Mohamed O. E. ;

Chencheri, Nidheesh ;

AlBanna, Ammar ;

Sultan, Meshal ;

El Bitar, Mohamed ;

Kherani, Safeena ;

Thalange, Nandu ;

Alshryda, Sattar ;

Di Donato, Roberto ;

Tzivinikos, Christos ;

Majid, Ibrar ;

Freeman, Alexandra F. F. ;

Gonzalez, Corina ;

Khan, Arif O. O. ;

Hamdan, Hisham ;

Abuhammour, Walid ;

AlAwadhi, Mohamed ;

AlKhayat, Abdulla ;

Alsheikh-Ali, Alawi ;

Abou Tayoun, Ahmad N. N. .

GENOME MEDICINE, 2023, 15 (01)

[9] ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing [J].

Green, Robert C. ;

Berg, Jonathan S. ;

Grody, Wayne W. ;

Kalia, Sarah S. ;

Korf, Bruce R. ;

Martin, Christa L. ;

McGuire, Amy L. ;

Nussbaum, Robert L. ;

O'Daniel, Julianne M. ;

Ormond, Kelly E. ;

Rehm, Heidi L. ;

Watson, Michael S. ;

Williams, Marc S. ;

Biesecker, Leslie G. .

GENETICS IN MEDICINE, 2013, 15 (07) :565-574

[10] Clinical utility of genomic sequencing: a measurement toolkit [J].

Hayeems, Robin Z. ;

Dimmock, David ;

Bick, David ;

Belmont, John W. ;

Green, Robert C. ;

Lanpher, Brendan ;

Jobanputra, Vaidehi ;

Mendoza, Roberto ;

Kulkarni, Shashi ;

Grove, Megan E. ;

Taylor, Stacie L. ;

Ashley, Euan .

NPJ GENOMIC MEDICINE, 2020, 5 (01)

← 1 2 3 →