Optimising the molecular investigation of the FSHD locus: an integrated workflow using single molecule optical mapping and Southern blot analysis
Year: 2025
Type: article
Study design: Observational Study
Abstract: PURPOSE: gene. FSHD cases often involve complex rearrangements, such as intrachromosomal rearrangements and translocations, which complicate diagnosis using conventional methods. This study focuses on evaluating the diagnostic potential of single molecule optical mapping (SMOM) for FSHD with complex rearrangements, particularly in cases involving 4q-10q translocations, which present challenges for detection by SMOM alone. Furthermore, we propose an integrated diagnostic strategy, combining SMOM with complementary methods, to improve accuracy in these challenging cases. METHODS: We reviewed the test results of 238 patients with suspected FSHD, and 25 participants with presumed complex rearrangements were included in this study. SMOM was performed on these participants, and the results were manually reviewed and compared with those obtained from Southern blot (SB) analysis. RESULTS: Nine patients carrying 4q-10q translocation exhibited discrepancies between the two methods. Linear regression analysis revealed a significant discrepancy in chromosomal assignment between SB and SMOM in cases suspected of translocation. CONCLUSIONS: Given the complex nature of FSHD, none of the current methods can independently provide a definitive diagnosis. As misdiagnosis may occur when relying on a single technique, we propose an integrated diagnostic approach, with SMOM as the first-line test.
Source: Journal of Medical Genetics
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Award: G4476671115
OpenAlex ID: W4409475954