Unraveling MECP2 structural variants in previously elusive Rett syndrome cases through IGV interpretation DOI Creative Commons
Tomer Poleg, Noam Hadar, Gali Heimer

et al.

npj Genomic Medicine, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 13, 2025

Rett syndrome (RTT) is a severe neurodevelopmental disorder, with MECP2 mutations accounting for 90–95% of classic and 50–70% atypical cases. However, many clinically diagnosed RTT patients remain without molecular diagnoses. While point large rearrangements in are well studied, the role small-intermediate structural variants (SVs) remains mostly elusive. Using standard short-read whole genome sequencing, we identified novel de novo SVs three out previously unresolved cases: complex SV two deletions ( ~ 5Kbp ~60Kbp) ~105Kbp inversion; ~200Kbp translocation; ~3Kbp deletion. These findings suggest that such elusive might be common cause "MECP2-negative" RTT. Incorporating detection into routine genetic testing through bioinformatic analysis sequencing or manual review using IGV could improve diagnostic rates expand our understanding similar disorders.

Language: Английский

Unraveling MECP2 structural variants in previously elusive Rett syndrome cases through IGV interpretation DOI Creative Commons
Tomer Poleg, Noam Hadar, Gali Heimer

et al.

npj Genomic Medicine, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 13, 2025

Rett syndrome (RTT) is a severe neurodevelopmental disorder, with MECP2 mutations accounting for 90–95% of classic and 50–70% atypical cases. However, many clinically diagnosed RTT patients remain without molecular diagnoses. While point large rearrangements in are well studied, the role small-intermediate structural variants (SVs) remains mostly elusive. Using standard short-read whole genome sequencing, we identified novel de novo SVs three out previously unresolved cases: complex SV two deletions ( ~ 5Kbp ~60Kbp) ~105Kbp inversion; ~200Kbp translocation; ~3Kbp deletion. These findings suggest that such elusive might be common cause "MECP2-negative" RTT. Incorporating detection into routine genetic testing through bioinformatic analysis sequencing or manual review using IGV could improve diagnostic rates expand our understanding similar disorders.

Language: Английский

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