Precision Genetics: Nanopore Sequencing Offers New Hope for Prenatal Diagnosis

Myotonic dystrophy type 1 (DM1) is a neurodevelopmental disorder caused by a genetic 'stutter'—a specific sequence of DNA (CTG) that repeats abnormally within the DMPK gene. Clinicians determine the severity of the condition by measuring the length of this expansion. However, the traditional method, Southern blotting, requires large amounts of genomic DNA, making it ill-suited for prenatal testing where samples are scarce.

Researchers have now evaluated Nanopore long-read sequencing (LRS) as a modern alternative. By utilising CRISPR/Cas9 technology to enrich the specific gene target, the team successfully detected and accurately sized expanded CTG repeats exceeding 1,000 units. This targeted approach proved far more efficient than using Adaptive Sampling alone.

While this is a breakthrough for prenatal diagnosis, challenges remain for preimplantation genetic diagnosis (PGD). The team discovered that using whole genome amplified DNA—a technique often necessary when working with microscopic samples like embryos—did not allow for reliable measurement of the repeat lengths. Consequently, whilst Nanopore sequencing shows immense potential to replace Southern blotting, further optimisation is required before it can be used for embryo screening.