Genetic testing included fragment analysis, gene panel analysis and exome sequencing, which only detected one pathogenic heterozygous missense variant (c.389 G>T,p.Gly130Val) in FXN. Although conventional repeat analyses failed to detect GAA expansions in our patient, subsequent short-read genome sequencing (GS) indicated a potential GAA repeat expansion. This finding was confirmed by long-read GS, which in addition revealed a complex pattern of interruptions. Both large and small GAA expansions with divergent interruptions containing G, A, GA, GAG and/or GAAG sequences were present within one allele, indicating mosaic sequence variations. Our findings underscore the complexity of repeat expansions which can exhibit both interruptions and somatic instability. We also highlight the utility of long-read GS in unraveling intricate genetic profiles, ultimately contributing to more accurate diagnoses in clinical practice.
Friday, May 23, 2025
Long-Read Sequencing Identifies Mosaic Sequence Variations in Friedreich’s Ataxia-GAA Repeats
Park, Joohyun, Claudia Dufke, Zofia Fleszar, Michael Schlotterbek, Elena Buena-Atienza, Lara G. Stühn, Caspar Gross, Marc Sturm, Stephan Ossowski, Ludger Schöls, and et al. 2025. "Long-Read Sequencing Identifies Mosaic Sequence Variations in Friedreich’s Ataxia-GAA Repeats" International Journal of Molecular Sciences 26, no. 11: 4969. doi:10.3390/ijms26114969
