[en] 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-∞, 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.
Disciplines :
Genetics & genetic processes
Author, co-author :
Thorpe, Erin ; Illumina Inc, San Diego, CA, USA
Williams, Taylor; Genetic and Genomic Services PBC, Houston, TX, USA
Shaw, Chad; Genetic and Genomic Services PBC, Houston, TX, USA, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA, Department of Statistics, Rice University, Houston, TX, USA
Chekalin, Evgenii; Illumina Inc, San Diego, CA, USA
Ortega, Julia; Illumina Inc, San Diego, CA, USA, C2N Diagnostics, St. Louis, MO, USA
Robinson, Keisha; Illumina Inc, San Diego, CA, USA
Button, Jason; Illumina Inc, San Diego, CA, USA
Jones, Marilyn C; Rady Children's Hospital, San Diego, CA, USA, University of California, San Diego, San Diego, CA, USA
Campo, Miguel Del; Rady Children's Hospital, San Diego, CA, USA, University of California, San Diego, San Diego, CA, USA
Basel, Donald; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA
McCarrier, Julie; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA
Keppen, Laura Davis; Sanford USD Medical Center, Sioux Falls, SD, USA
Royer, Erin; Sanford Children's Specialty Clinics at Sanford Health, USD Sanford School of Medicine, Sioux Falls, SD, USA
Foster-Bonds, Romina; Rare Genomics Institute, Los Angeles, CA, USA
Duenas-Roque, Milagros M; Servicio de Genética, Hospital Edgardo Rebagliati Martins - EsSalud, Lima, Peru
Urraca, Nora; University of Tennessee Health Science Center, Le Bonheur Children's Hospital, Memphis, TN, USA
Bosfield, Kerri; University of Tennessee Health Science Center, Le Bonheur Children's Hospital, Memphis, TN, USA
Brown, Chester W; University of Tennessee Health Science Center, Le Bonheur Children's Hospital, Memphis, TN, USA
Lydigsen, Holly; University of Tennessee Health Science Center, Le Bonheur Children's Hospital, Memphis, TN, USA
Mroczkowski, Henry J; University of Tennessee Health Science Center, Le Bonheur Children's Hospital, Memphis, TN, USA
Ward, Jewell; University of Tennessee Health Science Center, Le Bonheur Children's Hospital, Memphis, TN, USA
Sirchia, Fabio; Department of Molecular Medicine, University of Pavia, Pavia, Italy, Medical Genetics Unit, IRCCS San Matteo Foundation, Pavia, Italy
Giorgio, Elisa; Department of Molecular Medicine, University of Pavia, Pavia, Italy, Medical Genetics Unit, IRCCS Mondino Foundation, Pavia, Italy
Vaux, Keith; Point Loma Pediatrics, San Diego, CA, USA
Salguero, Hildegard Peña; Padrino Children's Foundation, Todos Santos, B.C.S., Mexico
Lumaka, Aimé ; Centre de Genetique Humaine, Universite de Kinshasa, Kinshasa, Democratic Republic of the Congo, Center for Human Genetics, Centre Hospitalier Universitaire, Liège, Belgium
Mubungu, Gerrye; Centre de Genetique Humaine, Universite de Kinshasa, Kinshasa, Democratic Republic of the Congo
Makay, Prince; Centre de Genetique Humaine, Universite de Kinshasa, Kinshasa, Democratic Republic of the Congo
Ngole, Mamy; Centre de Genetique Humaine, Universite de Kinshasa, Kinshasa, Democratic Republic of the Congo
Lukusa, Prosper Tshilobo; Centre de Genetique Humaine, Universite de Kinshasa, Kinshasa, Democratic Republic of the Congo
Vanderver, Adeline; Division of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Muirhead, Kayla; Ambry Genetics, Aliso Viejo, CA, USA
Sherbini, Omar; Division of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA
Lah, Melissa D; Indiana University School of Medicine, Indianapolis, IN, USA
Anderson, Katelynn; Indiana University School of Medicine, Indianapolis, IN, USA
Bazalar-Montoya, Jeny; Instituto Nacional de Salud del Niño-San Borja, Lima, Peru
Rodriguez, Richard S; Instituto Nacional de Salud del Niño-San Borja, Lima, Peru
Cornejo-Olivas, Mario; Neurogenetics Research Center, Instituto Nacional de Ciencias Neurologicas, Lima, Peru, Neurogenetics Working Group, Universidad Científica del Sur, Lima, Peru
Milla-Neyra, Karina; Neurogenetics Research Center, Instituto Nacional de Ciencias Neurologicas, Lima, Peru
Shinawi, Marwan; Washington University, St. Louis, MO, USA, St. Louis Children's Hospital, St. Louis, MO, USA
Magoulas, Pilar; Texas Children's Hospital, Houston, TX, USA
Henry, Duncan; UCSF Benioff Children's Hospitals, San Francisco, CA, USA
Gibson, Kate; Canterbury District Health Board, Canterbury, New Zealand
Jayakar, Parul; Nicklaus Children's Health System, Miami, FL, USA
Salyakina, Daria; Nicklaus Children's Health System, Miami, FL, USA
Masser-Frye, Diane; Rady Children's Hospital, San Diego, CA, USA, San Diego-Imperial Counties Developmental Services, Inc., San Diego, CA, USA
Serize, Arturo; South Miami Hospital, South Miami, FL, USA
Perez, Jorge E; South Miami Hospital, South Miami, FL, USA
Taylor, Alan; Al Jalila Genomics Center of Excellence, Al Jalila Children's Specialty Hospital, Dubai, United Arab Emirates
Shenbagam, Shruti; Al Jalila Genomics Center of Excellence, Al Jalila Children's Specialty Hospital, Dubai, United Arab Emirates
Abou Tayoun, Ahmad; Al Jalila Genomics Center of Excellence, Al Jalila Children's Specialty Hospital, Dubai, United Arab Emirates, Center for Genomic Discovery, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
Malhotra, Alka; Illumina Inc, San Diego, CA, USA
Bennett, Maren; Illumina Inc, San Diego, CA, USA
Rajan, Vani; Illumina Inc, San Diego, CA, USA, Veracyte, San Diego, CA, USA
Avecilla, James; Illumina Inc, San Diego, CA, USA
Warren, Andrew; Illumina Inc, San Diego, CA, USA
Arseneault, Max; Illumina Inc, San Diego, CA, USA
Kalista, Tasha; Illumina Inc, San Diego, CA, USA
Crawford, Ali; Illumina Inc, San Diego, CA, USA
Ajay, Subramanian S; Illumina Inc, San Diego, CA, USA
Perry, Denise L; Illumina Inc, San Diego, CA, USA
Belmont, John; Genetic and Genomic Services PBC, Houston, TX, USA
Taft, Ryan J; Illumina Inc, San Diego, CA, USA. Electronic address: rtaft@geneticalliance.org
The impact of clinical genome sequencing in a global population with suspected rare genetic disease.
Publication date :
2024
Journal title :
American Journal of Human Genetics
ISSN :
0002-9297
eISSN :
1537-6605
Publisher :
Cell Press, United States
Volume :
111
Issue :
7
Pages :
1271 - 1281
Peer reviewed :
Peer Reviewed verified by ORBi
Funding text :
We thank the families for their participation in iHope. Illumina acknowledges Sylwia Urbaniak and Joey Flores, Illumina Laboratory Services inclusive of the software, bioinformatics, and interpretation teams, and shipping and logistics. Instituto Nacional de Ciencias Neurol\u00F3gicas Per\u00FA acknowledges Elison Sarapura-Castro, Andrea Rivera-Valdivia, Jorge La Serna, and the Neurogenetics DNA Bank team. M.C.-O. was supported by Universidad Cient\u00EDfica del Sur through RD Nr. 009-DGIDI-CIENTIFICA-2023 . Edgardo Rebagliati Martins National Hospital acknowledges Nelson Purizaca and Ana Protzel and the cytogenetics laboratory staff. The University of Kinshasa acknowledges Laetitia Mavinga, Dahlie Tshika, Nadine Nsiangani, Cathy Songo, and Chlo\u00E9 Musuamba. A.L.Z., G.M., P. Makay, M.N., and P.L. were supported by NHGRI R01HG012284 and NIMH U01MH115483 . The University of Tennessee Health Science Center and Le Bonheur Children\u2019s Hospital acknowledges Megan Fonville, MS, CGC, Emma Bradley, MS, CGC, Roya Mostafavi, MS, CGC, and Shannon Holtrop, MS, CGC. The University of Pavia clinical team was supported by NEXTGENERATIONEU( NGEU ) and funded by the Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP), project MNESYS ( PE0000006 ) \u2013 A Multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553 11.10.2022). A.V. receives grants and in-kind support from Eli Lilly , Gilead , Takeda , Illumina , Biogen , Boehringer Ingelheim , Sanofi , Sana , Myrtelle , Affinia , Homology , Ionis , Passage Bio , and Orchard Therapeutics . A.V. serves on the scientific advisory boards of the MLD Foundation, European Leukodystrophy Association, and the United Leukodystrophy Foundation and in an unpaid capacity for Takeda, Ionis, Biogen, and Illumina.
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