The genomic landscape of pediatric rheumatology disorders in the Middle East. Issue 4 (7th February 2021)

• Record Type: Journal Article
• Authors: Fathalla, Basil M.; Alsarhan, Ali; Afzal, Samina; El Naofal, Maha; Abou Tayoun, Ahmad
• Is Part Of: Human mutation. Volume 42:Issue 4(2021)
• Page Start: e1
• Page End: e14
• Publication Date: 2021-02-07
• Subjects: diagnostic yield -- exome sequencing -- genomics -- next‐generation sequencing -- rheumatology; Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.24165
• Languages: English
• ISSNs: 1059-7794

Abstract

Abstract: The landscape and clinical utility of comprehensive genomic investigations for a wide range of pediatric rheumatic disorders have not been fully characterized in the Middle East. Here, 71 pediatric patients, of diverse Arab origins, were clinically and genetically assessed for a spectrum of rheumatology‐related diseases at the only dedicated tertiary children's hospital in the United Arab Emirates. Clinical genomic investigations included mainly (76%) next‐generation sequencing‐based gene panels and whole‐exome sequencing, along with rapid sequencing in the intensive care unit and urgent setting. The overall positive yield was 46.5%, whereas dual diagnoses were made in two cases (3%). Although the majority (21/33, 64%) of positive findings involved the MEFV gene, the remaining (12/33, 36%) alterations were attributed to 11 other genes/loci. Copy number variants (CNVs) contributed substantially (5/33, 15.2%) to the overall diagnostic yield. Sequencing‐based testing, specifically rapid sequencing, had a high positive rate and delivered timely results. Genetic findings guided clinical management plans and interventions in most cases (27/33, 81.8%). We highlight unique findings and provide additional evidence that heterozygous loss of function of the IFIH1 gene increases susceptibility to recurrent fevers. Our study provides new insights into the pathogenic variation landscape in pediatric rheumatic disorders. Abstract : We characterize the genomic landscape of pediatric rheumatology disorders in a pediatric Arab patient population from the Middle East. Genomic investigations included next generation sequencing based testing including targeted gene panels and family‐based whole exome sequencing. Diagnostic yield was 46.5%, and management was alerted in 82% of positive cases. Copy number variants contributed 15.2% of all positive cases, and while 64% of pathogenic variants were in the MEFV, the remaining 36% (11/33) were distributed across 11 genes/loci.