From birth, Zoé Berman exhibited atypical symptoms. “Zoé couldn’t suck,” her mother, Sarah Berman recalls. “She was just kind of limp and open-mouthed. She didn’t really cry. She had low muscle tone.[1]” Upon clinical evaluation, neurologists diagnosed her with myotonic dystrophy (DM1), a genetic and progressive muscular disorder that affects multiple body systems. “They had Sarah do the handshake test,” says Zoé’s father, David, to see how long it would take her to relax her grip after shaking hands with a doctor, “and that made them even more confident in their diagnosis.[2]”
DM1 is classified as a repeat expansion disorder, resulting from abnormal repeat expansions of three nucleotides (cytosine-thymine-guanine) in the gene DMPK, which provides a blueprint for various muscles in the human body[3]. Diagnosing this disease is challenging due to the complexity of repetitive sequences[4] and the technical challenges of properly identifying and quantifying expansions within the human genome. Methods, such as Southern blotting or polymerase chain reaction (PCR) tests, can detect larger repeats within the genome but are limited by their cost, turnaround time, and low sensitivity.
Looking for a more accurate and cost-effective way to diagnose triplet-repeat diseases like DM1, researchers at the University of Tokyo developed their own CRISPR-based diagnostic technology, REPLICA[5]. REPLICA (Repeat Primed Locating of Inherited disease by Cas3) is a novel method for diagnosing DM1 that offers superior sensitivity and specificity through the use of Cas DNA-recognition enzymes to rapidly visualize repetitive sequences as “bands,” similar to an over-the-counter COVID-19 or influenza test. The precision of this method allows for the robust detection of repeat length, which is correlated with disease severity. Using samples from DM1 patients and unaffected individuals from the NIGMS repository at Coriell, these researchers created a technique that enables efficient, accessible screening to identify patients with undiagnosed triplet-repeat diseases. Future applications of this technology may allow for more efficient and effective automation of DM1 blood-sample detection, and potentially revolutionize genetic disease screening.
Since its publication, this study has been cited in ongoing research related to diagnostic methods and clinical developments, including investigations into Charcot-Marie-Tooth disease, a group of inherited disorders that cause peripheral nerve damage[6].
Established in 1972, the NIGMS Human Genetic Cell Repository at Coriell contains some of the most scientifically impactful and widely-used cell lines globally, representing a broad spectrum of disease states, chromosomal abnormalities, and diverse human populations. In addition, Coriell hosts five other NIH-funded biobanks, distributes thousands of samples each year, and provides research and biobanking services to scientists worldwide.
[1] Myotonic Dystrophy Foundation. (2025, December 29). Families helping families: Sarah and David Berman. Myotonic Dystrophy Foundation. https://myotonic.org/family-stories/families-helping-families-sarah-and-david-berman/?_gl=1%2Awk6j4m%2A_gcl_au%2ANzkxNDM0ODQwLjE3ODExMTY1Nzg.%2A_ga%2ANzUzMzE2MDY4LjE3ODExMTY1Nzg.%2A_ga_SH4QXJHEVZ%2AczE3ODExMTY1NzckbzEkZzEkdDE3ODExMTgzODEkajU5JGwwJGgw
[2] Myotonic Dystrophy Foundation. (2025, December 29). Families helping families: Sarah and David Berman. Myotonic Dystrophy Foundation. https://myotonic.org/family-stories/families-helping-families-sarah-and-david-berman/?_gl=1%2Awk6j4m%2A_gcl_au%2ANzkxNDM0ODQwLjE3ODExMTY1Nzg.%2A_ga%2ANzUzMzE2MDY4LjE3ODExMTY1Nzg.%2A_ga_SH4QXJHEVZ%2AczE3ODExMTY1NzckbzEkZzEkdDE3ODExMTgzODEkajU5JGwwJGgw
[3] Ramakrishnan S, Gupta V. Trinucleotide Repeat Disorders. [Updated 2024 Dec 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559254/
[4] Koji Asano, Kazuto Yoshimi, Kohei Takeshita, Satomi Mitsuhashi, Yuta Kochi, Rika Hirano, Zong Tingyu, Saeko Ishida, and Tomoji Mashimo. CRISPR Diagnostics for Quantification and Rapid Diagnosis of Myotonic Dystrophy Type 1 Repeat Expansion Disorders. ACS Synthetic Biology 2024 13 (12), 3926-3935. DOI: 10.1021/acssynbio.4c00265
[5] Koji Asano, Kazuto Yoshimi, Kohei Takeshita, Satomi Mitsuhashi, Yuta Kochi, Rika Hirano, Zong Tingyu, Saeko Ishida, and Tomoji Mashimo. CRISPR Diagnostics for Quantification and Rapid Diagnosis of Myotonic Dystrophy Type 1 Repeat Expansion Disorders. ACS Synthetic Biology 2024 13 (12), 3926-3935. DOI: 10.1021/acssynbio.4c00265
[6] De Grado, A., Serio, M., Saveri, P., Pisciotta, C., & Pareyson, D. (2025). Charcot-Marie-Tooth disease: a review of clinical developments and its management - What’s new in 2025? Expert Review of Neurotherapeutics, 25(4), 427–442. https://doi.org/10.1080/14737175.2025.2470980
