From the start, CeGaT’s 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.”, explains Dr. Florian Battke, Director of Development at CeGaT, and emphasizes: “That‘s where our ExomeXtra® enrichment steps in. Now, it 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, fifth disease, syphilis, and herpes simplex virus types 1 and 2. These infections are non-genetic and typically undetected by standard exome sequencing, which can lead to abnormal ultrasound findings and might have serious consequences for fetal development. Incorporating this screening enables early identification and intervention.

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

“At CeGaT, we are committed to incorporating the latest scientific findings and adapting our exome diagnostics to find the cause of every genetic disease.“, states Dr. Dirk Biskup, Managing Director and Co-founder of CeGaT. “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.” CeGaT has 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, including SCA1 (ATXN1), SCA2 (ATXN2), SCA3 (ATXN3), SCA6 (CACNA1A), SCA7 (ATXN7), CSTB, FGF14², HTT, JPH3, NOP56, NIPA1, PABPN1, and others.