Upgrade of ExomeXtra® for Even More Comprehensive Diagnostics

November 14, 2024

We are excited to announce significant advancements in exome diagnostics with the latest update to our ExomeXtra® enrichment. The new update is a further step forward in providing innovative solutions to improve patient care.

From the start, our ExomeXtra® pushed genetic diagnostics beyond the coding regions analyzed by off-the-shelf exomes, adding coverage for non-coding variants and introducing a genomic backbone for whole-genome CNV calling. The newest version 6 of ExomeXtra® further expands its capabilities by incorporating all non-coding splice sites as well as all non-coding RNAs involved in the splicing process. Additionally, the inclusion of screening for relevant infections broadens ExomeXtra®’s diagnostic scope for prenatal diagnostics.

Inclusion of non-coding splice sites and all snRNAs in both spliceosomes, including RNU4-2

Splicing defects can lead to serious consequences. However, conventional exome diagnostics overlook relevant variants if they are located in non-coding, untranslated exons. Plus, non-coding spliceosomal RNAs are usually not analyzed. Therefore, our ExomeXtra® enrichment now covers all small nuclear RNAs (snRNAs) of both spliceosomes, with a specific focus on RNU4-2. A recent publication1 has identified RNU4-2 as a frequent cause of syndromic neurodevelopmental disorders, underscoring the importance of its inclusion.

Introduction of prenatal infection screening

Recognizing the impact of prenatal infections on fetal health, the latest version of ExomeXtra® introduces screening for infections such as toxoplasmosis, varicella, cytomegalovirus, fifth disease, syphilis, and herpes simplex virus types 1 and 2. These infections are non-genetic and typically undetected by standard exome sequencing.

Improved backbone for array-like CNV detection and increased number of non-coding variants

With this update, we have expanded our coverage of disease-associated non-coding variants to over 46,000 targeted regions. ExomeXtra® is the only exome offering complete coverage of relevant variants from the ClinVar and HGMD databases. Also, we have strengthened the CNV backbone for array-like detection of copy number variation (CNV) in the whole genome by adding probes, thereby increasing its density around coding genes. Moreover, coverage has expanded to genes with repeat expansions linked to neuromuscular and neurodegenerative disorders.

Benefit from our unique service and offer your patients the “Xtra” in exome diagnostics. For more information about CeGaT’s ExomeXtra®, please visit our website or contact us at diagnostic-support@cegat.com.

References:

1 Chen, Y., Dawes, R., Kim, H.C. et al. De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome. Nature 632, 832–840 (2024).