GENOMICS


Automating familial hypercholesterolaemia genetic testing


Silvia Borras of NHS Grampian – part of the Scottish Strategic Network for Genomic Medicine – writes for Pathology in Practice, describing her laboratory’s experience of scaling up and automating its genetic testing for familial hypercholesterolaemia.


Familial hypercholesterolaemia (FH) is an inherited condition characterised by significantly elevated levels of low- density lipoprotein cholesterol (LDL-C), substantially increasing the risk of early coronary heart disease. With an estimated prevalence of around 1 in 250 worldwide, accurate and efficient genetic testing is crucial for early diagnosis, treatment optimisation, and family screening. At NHS Grampian, our genetics


laboratory is part of the Scottish Strategic Network for Genomic Medicine, delivering diagnostic testing for rare and inherited disorders and cancer for the local population of north-east Scotland, Orkney, and Shetland, and also providing a range of genomic services nationwide. Annually, we handle approximately 14,000 samples, of which more than 1,000 are referred specifically for FH screening, one of our national service responsibilities.


Scaling up: our move to NGS Since 2008, we’ve provided genetic testing for FH, initially using Sanger sequencing combined with Multiplex Ligation- dependent Probe Amplification (MLPA). Although highly reliable, these methods required substantial staff time and were not scalable enough to meet rapidly increasing demand, which surged to 700–800 annual tests within a few years. In response to escalating test volumes


and resource constraints, we transitioned to next-generation sequencing (NGS) in


2016, adopting an amplicon-based assay. While NGS improved throughput and enabled some automation, the original workflow required considerable manual intervention and multiple processing steps per sample, limiting efficiency. NGS has increasingly become the standard


for FH diagnostics due to its ability to comprehensively assess relevant genes, such as LDLR, APOB, APOE and PCSK9, and to detect rare and novel variants with high sensitivity and specificity.1,2


NGS panels now enable simultaneous detection of single nucleotide variants


Moreover,


Next-generation sequencing has increasingly become the standard for familial hypercholesterolaemia diagnostics due to its ability to comprehensively assess relevant genes.


September 2026 WWW.PATHOLOGYINPRACTICE.COM 39


AdobeStock / Marcin Janiec


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