Resolving a complex GPIHBP1 exons 3-4 deletion adjacent to low-complexity repeats using adaptive sampling long-read sequencing in familial chylomicronaemia.

3.5 kb homozygous deletion in a low-complexity repeat region, resolved by nanopore adaptive sampling

A patient with familial chylomicronaemia (triglycerides 100.6 mmol/L, eruptive xanthomata) had a homozygous GPIHBP1 exons 3–4 deletion, but long-range PCR failed to identify breakpoints in a cytosine-rich repeat region. PCR-free nanopore long-read sequencing with adaptive sampling enriched the GPIHBP1 locus to 88× coverage (vs 30× without enrichment), identifying a 3.5 kb homozygous deletion (NC_000008.11:g.143214459_143217987del). The 3' breakpoint lies within a VNTR region with degenerate 12-nucleotide subunits, explaining the failure of conventional PCR-based methods.

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This case perfectly illustrates the value of nanopore adaptive sampling for resolving SVs in genomically complex regions where conventional methods fail. It is the first complete characterization of this GPIHBP1 deletion by native long-read sequencing. For laboratories, adaptive sampling represents a cost-effective alternative to full long-read WGS for targeting specific difficult loci.

Clinical impact: 2/3 · Evidence quality: 2/3 · Novelty: 2/2 · Sample size: 0/1 · Journal quality: 0/1 → Total: 6/10