Faculty Collaboration Database

The impact of clinical genome sequencing in a global population with suspected rare genetic disease. Am J Hum Genet 2024 Jul 11;111(7):1271-1281

Date

06/07/2024

Pubmed ID

38843839

Pubmed Central ID

PMC11267518

DOI

10.1016/j.ajhg.2024.05.006

Scopus ID

2-s2.0-85197069117 (requires institutional sign-in at Scopus site)   1 Citation

Abstract

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.

Author List

Thorpe E, Williams T, Shaw C, Chekalin E, Ortega J, Robinson K, Button J, Jones MC, Campo MD, Basel D, McCarrier J, Keppen LD, Royer E, Foster-Bonds R, Duenas-Roque MM, Urraca N, Bosfield K, Brown CW, Lydigsen H, Mroczkowski HJ, Ward J, Sirchia F, Giorgio E, Vaux K, Salguero HP, Lumaka A, Mubungu G, Makay P, Ngole M, Lukusa PT, Vanderver A, Muirhead K, Sherbini O, Lah MD, Anderson K, Bazalar-Montoya J, Rodriguez RS, Cornejo-Olivas M, Milla-Neyra K, Shinawi M, Magoulas P, Henry D, Gibson K, Wiafe S, Jayakar P, Salyakina D, Masser-Frye D, Serize A, Perez JE, Taylor A, Shenbagam S, Abou Tayoun A, Malhotra A, Bennett M, Rajan V, Avecilla J, Warren A, Arseneault M, Kalista T, Crawford A, Ajay SS, Perry DL, Belmont J, Taft RJ

Author

Donald Basel MD Chief, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Child
Child, Preschool
Female
Genetic Diseases, Inborn
Genetic Testing
Humans
Infant
Male
Rare Diseases
Whole Genome Sequencing