Comprehensive molecular genetic testing is key to support early and accurate diagnosis of hereditary and rare diseases.

Fluorescence in situ hybridisation plays a vital role in the diagnosis of constitutional, hereditary, and rare diseases by enabling the direct visualisation of specific chromosomal abnormalities – such as microdeletions, duplications, or translocations. FISH probes provide a robust, validated method for detecting structural cytogenetic alterations that contribute to disease phenotypes and guide both genetic counselling and targeted management strategies. Because rare syndromes often depend on the identification of subtle structural aberrations, FISH remains a gold-standard complement to microarray or sequencing approaches when precise locus visualisation is required.

CytoCell^®’s carefully designed probes allow laboratories to detect these recurrent, clinically relevant changes with high specificity and signal clarity also in constitutional cytogenetics samples. CytoCell^® probes deliver practical benefits to diagnostic workflows: they are ready-to-use, pre-labelled, and designed for high signal intensity with minimal background, reducing the need for repeat testing and improving turnaround times.

Microarrays offer a powerful, genome-wide approach to detect copy number variations (CNVs) and other structural genomic alterations that underpin many genetic disorders. Unlike traditional karyotyping, which identifies only large chromosomal changes, or sequencing methods that primarily detect single nucleotide variants, microarrays bridge the gap by providing high-resolution insight into submicroscopic deletions, duplications, and regions of homozygosity across the entire genome. This capability is particularly valuable in uncovering the genetic basis of complex or unexplained developmental, neurological, and congenital conditions. In clinical research, microarray-based comparative genomic hybridisation (aCGH) has significantly increased the amount of clinically relevant information available, supporting earlier insights, more precise case evaluation, improved patient management, and better-informed genetic counselling. As a result, microarrays have become a first-tier methodology in many genetics laboratories and continue to play a crucial role alongside next-generation sequencing and FISH analysis.

CytoSure^® arrays further enhance precision by targeting genes implicated in specific metabolic or genetic disorders with increased exon-level coverage over clinically relevant regions* [1] .

Next-generation sequencing (NGS) complements and extends the capabilities of array- and FISH-based methods. While microarrays commonly excel at detecting genome-wide copy number changes and FISH provides targeted visual confirmation of specific chromosomal abnormalities, NGS enables comprehensive analysis of single-nucleotide variants, small insertions/deletions. This expanded capability of NGS is particularly valuable in the field of hereditary and rare diseases, where many rare conditions are caused by subtle structural aberrations (such as single-exon deletions) or by combinations of SNVs and CNVs. By unifying multiple variant-detection capabilities, NGS offers a broader, more detailed picture of the underlying genetic landscape.

The 700-gene CytoSure^® Constitutional NGS panel delivers CNV analysis down to single-exon level and loss of heterozygosity (LOH) as well as mosaicism, SNV and indel detection all in a single assay. The CytoSure^® Constitutional NGS solution includes the key strengths from the well-established CytoSure microarray brand, namely, the most up-to-date ID/DD content, expert panel design, class-leading complimentary software and unparalleled support. It enables the seamless transition from microarrays to NGS, delivering a significant increase in information obtained from a single assay without extensive analysis time and costly data generation and storage.