Chromosomal microarray analysis supplements exome sequencing to diagnose children with suspected inborn errors of immunity.

Though copy number variants (CNVs) have been suggested to play a significant role in inborn errors of immunity (IEI), the precise nature of this role remains largely unexplored. We sought to determine the diagnostic contribution of CNVs using genome-wide chromosomal microarray analysis (CMA) in children with IEI. We performed exome sequencing (ES) and CMA for 332 unrelated pediatric probands referred for evaluation of IEI. The analysis included primary, secondary, and incidental findings. Of the 332 probands, 134 (40.4%) received molecular diagnoses. Of these, 116/134 (86.6%) were diagnosed by ES alone. An additional 15/134 (11.2%) were diagnosed by CMA alone, including two likely Pairing ES and CMA can provide a comprehensive evaluation to clarify the complex factors that contribute to both immune and non-immune phenotypes. Such a combined approach to genetic testing helps untangle complex phenotypes, not only by clarifying the differential diagnosis, but in some cases by identifying multiple diagnoses contributing to the overall clinical presentation.

Informations de copyright

Copyright © 2023 Beers, Similuk, Ghosh, Seifert, Jamal, Kamen, Setzer, Jodarski, Duncan, Hunt, Mixer, Cao, Bi, Veltri, Karlins, Zhang, Li, Oler, Jevtich, Yu, Hullfish, Bielekova, Frischmeyer-Guerrerio, Dang Do, Huryn, Olivier, Su, Lyons, Zerbe, Rao, Keller, Freeman, Holland, Franco, Walkiewicz and Yan.

Déclaration de conflit d'intérêts

WB is an employee of Baylor Genetics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer IC declared a shared affiliation, with no collaboration, with one of the authors, WB, to the handling editor at the time of the review.