New study published in The Journal of Molecular Diagnostics paves the way for population-based screening for monogenic autism spectrum disorder and better informed genetic counseling

Philadelphia, June 12, 2025 – Researchers have developed an innovative new nanopore sequencing assay to identify carriers of fragile X syndrome (FXS), the leading cause of monogenic autism spectrum disorder and inherited intellectual disabilities. The study in The Journal of Molecular Diagnostics, published by Elsevier, addresses the urgent need for a screening tool to identify carriers of FXS in a more comprehensive, faster, efficient, and cost-effective way compared to current methods, for better informed genetic counseling.

FXS affects approximately 1 in 7000 females and 1 in 4000 males worldwide. Common characteristics include mild to severe intellectual disability, developmental delays in speech and motor skills, behavioral and social issues such as ADHD-like and autism spectrum disorder symptoms, sensory sensitivities, and sometimes characteristic physical features.

Lead investigator Qiwei Guo, PhD, Department of Central Laboratory, Department of Obstetrics and Gynecology, Fujian Key Clinical Specialty of Laboratory Medicine, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, China, says, “Although FXS carrier prevalence is high, with all major ethnic groups and races being susceptible to FXS, widespread FXS carrier screening for the general population has remained debatable. Based on previous research, clinical interest has shifted from ‘whether to perform’ to ‘how to perform’ population-based FXS carrier screening. However, an accurate, fast, affordable, and effective carrier screening assay that can examine a large number of female samples was still lacking. In this study, we developed a reliable and user-friendly software to analyze sequencing data and report results.”

The gene responsible for FXS is fragile X messenger ribonucleoprotein1 (FMR1), an X-linked dominant gene with full penetrance in all males and many females. It plays a crucial role in synapse formation and normal dendrite development. The number of CGG repeats, a specific sequence of DNA building blocks, is a key indicator of whether someone has a normal FMR1 gene, carries a premutation, or has the full mutation that causes FXS.

Co-investigator Yulin Zhou, PhD, Department of Central Laboratory, Department of Obstetrics and Gynecology, Fujian Key Clinical Specialty of Laboratory Medicine, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, China, explains, “We demonstrated that the nanopore sequencing assay can accurately identify the full range of premutation FMR1 alleles, which account for the majority of FXS carriers, and the nanopore sequencing assay was able to reliably quantify CGG repeats and AGG interruptions, two specific DNA sequence variations that are critical for determining the risk of full mutation expansion in carriers, thus facilitating genetic counseling for carrier screening.”

By utilizing identifier sequences, the researchers were able to test multiple samples in a single assay, dramatically increasing test capacity and reducing costs. The nanopore sequencing assay can be accomplished within a short turnaround time (approximately two days for an assay testing 100 simultaneously) by a technician in a standard molecular diagnostics laboratory. Compared to other commonly used techniques, the equipment for nanopore sequencing assays is more accessible and portable, and thus could be more readily and widely adapted, particularly in underdeveloped regions of the world.

Dr. Guo concludes, “We focus on controlling human genetic diseases and reducing birth defects. Given the significant morbidity associated with FXS and the lack of effective treatments, prenatal diagnosis and intervention are warranted. Our findings demonstrate that this novel nanopore sequencing assay overcomes key limitations of existing methods for FXS carrier screening, ultimately paving the way for enhanced genetic counseling and broader implementation worldwide.”