Traditional DNA tests may overlook 10% of classic in Familial Adenomatous Polyposis (FAP) cases. By integrating RNA sequencing, researchers unveiled novel APC variants in six families, explaining missed diagnoses due to abnormal gene splicing. The approach, DNA-RNA multigene panel testing, enhances detection rates, guiding family planning and treatment for FAP patients. Read more about this under Article 1 below.
Contents
- Article 1: Solving missing heritability in patients with Familial Adenomatous Polyposis with DNA-RNA paired testing
- Article 2: Exome copy number variant detection, analysis, and classification in a large cohort of families with undiagnosed rare genetic disease
- Article 3: A genome-wide spectrum of tandem repeat expansions in 338,963 humans
- Article 4: Clinical effectiveness of newborn screening for Spinal Muscular Atrophy: A nonrandomized controlled trial
- References
Article 1: Solving missing heritability in patients with Familial Adenomatous Polyposis with DNA-RNA paired testing
This study investigates patients with hereditary colorectal cancer predisposition due to APC gene variants. Traditional DNA-only testing may miss up to 10% of classic familial adenomatous polyposis (FAP) cases. By adding RNA sequencing alongside DNA testing, researchers identified novel APC variants in six families. These variants caused abnormal gene splicing, explaining missed diagnoses. The approach, called paired DNA-RNA multigene panel testing, improves detection rates, aiding in family planning and treatment decisions for FAP patients and families. Read the full article here.
In summary: Paired DNA-RNA testing improves detection of APC variants in familial adenomatous polyposis
Article 2: Exome copy number variant detection, analysis, and classification in a large cohort of families with undiagnosed rare genetic disease
Researchers utilized advanced methods to detect copy number variants (CNVs) from exome sequencing data in 6,633 families with rare genetic diseases. They identified 171 families (2.6%) with causal CNVs, ranging from small deletions to complex structural variants. Using established guidelines and additional criteria, they classified 151 CNVs as likely pathogenic/pathogenic and 20 as variants of uncertain significance. This approach enhances diagnostic yield for undiagnosed cases, offering a cost-effective alternative to genome sequencing and improving CNV pathogenicity assessment. Read the full article here.
In summary: Advanced CNV detection enhances diagnostic yield in rare genetic diseases
Article 3: A genome-wide spectrum of tandem repeat expansions in 338,963 humans
The Genome Aggregation Database (gnomAD) has been a vital resource for understanding human genetic variation. However, it has largely overlooked tandem repeat (TR) expansions, despite their association with over 50 human diseases. This study introduces TR-gnomAD, a reference of 0.86 million TRs from diverse whole-genome sequencing samples. TR-gnomAD reveals ancestry-specific disease patterns and distinguishes between common and potentially harmful TR expansions, aiding researchers and physicians in interpreting TR-related genetic diseases. Access TR-gnomAD at https://wlcb.oit.uci.edu/TRgnomAD. Read the full article here.
In summary: TR-gnomAD: A new resource for understanding tandem repeat expansions
Article 4: Clinical effectiveness of newborn screening for Spinal Muscular Atrophy: A nonrandomized controlled trial
Early detection and treatment are crucial for spinal muscular atrophy (SMA) outcomes. This study compared infants diagnosed through newborn screening with those diagnosed after symptoms appeared. Analyzing data from 234 children, it found those screened at birth achieved motor milestones better than clinically diagnosed infants. Most newborn-screened infants gained independent sitting and walking abilities, highlighting the effectiveness of newborn screening in improving SMA outcomes. This emphasizes the importance of early detection programs for better management of SMA. Read the full article here.
In summary: Early detection improves outcomes in spinal muscular atrophy
References
[1] Young, C. C., Horton, C., Grzybowski, J., Abualkheir, N., Ramirez Castano, J., Molparia, B., Karam, R., Chao, E., & Richardson, M. E. (2024). Solving Missing Heritability in Patients With Familial Adenomatous Polyposis With DNA-RNA Paired Testing. JCO precision oncology, 8, e2300404. https://doi.org/10.1200/PO.23.00404
[2] Lemire, G., Sanchis-Juan, A., Russell, K., Baxter, S., Chao, K. R., Singer-Berk, M., Groopman, E., Wong, I., England, E., Goodrich, J., Pais, L., Austin-Tse, C., DiTroia, S., O’Heir, E., Ganesh, V. S., Wojcik, M. H., Evangelista, E., Snow, H., Osei-Owusu, I., Fu, J., … O’Donnell-Luria, A. (2024). Exome copy number variant detection, analysis, and classification in a large cohort of families with undiagnosed rare genetic disease. American journal of human genetics, S0002-9297(24)00081-8. Advance online publication. https://doi.org/10.1016/j.ajhg.2024.03.008
[3] Cui, Y., Ye, W., Li, J. S., Li, J. J., Vilain, E., Sallam, T., & Li, W. (2024). A genome-wide spectrum of tandem repeat expansions in 338,963 humans. Cell, S0092-8674(24)00252-6. Advance online publication. https://doi.org/10.1016/j.cell.2024.03.004
[4] Schwartz, O., Vill, K., Pfaffenlehner, M., Behrens, M., Weiß, C., Johannsen, J., Friese, J., Hahn, A., Ziegler, A., Illsinger, S., Smitka, M., von Moers, A., Kölbel, H., Schreiber, G., Kaiser, N., Wilichowski, E., Flotats-Bastardas, M., Husain, R. A., Baumann, M., Köhler, C., … SMARTCARE study group (2024). Clinical Effectiveness of Newborn Screening for Spinal Muscular Atrophy: A Nonrandomized Controlled Trial. JAMA pediatrics, 10.1001/jamapediatrics.2024.0492. Advance online publication. https://doi.org/10.1001/jamapediatrics.2024.0492
