PT  - JOURNAL ARTICLE
AU  - Dremsek, Paul
AU  - Schachner, Anna
AU  - Reischer, Theresa
AU  - Krampl-Bettelheim, Elisabeth
AU  - Bettelheim, Dieter
AU  - Vrabel, Sybille
AU  - Delissen, Zoja
AU  - Pfeifer, Mateja
AU  - Weil, Beatrix
AU  - Bajtela, Robert
AU  - Hengstschläger, Markus
AU  - Laccone, Franco
AU  - Neesen, Jürgen
TI  - Retrospective study on the utility of optical genome mapping as a follow-up method in genetic diagnostics
AID  - 10.1136/jmg-2024-110265
DP  - 2025 Feb 01
TA  - Journal of Medical Genetics
PG  - 89--96
VI  - 62
IP  - 2
4099  - http://jmg.bmj.com/content/62/2/89.short
4100  - http://jmg.bmj.com/content/62/2/89.full
SO  - J Med Genet2025 Feb 01; 62
AB  - Background Current standard-of-care (SOC) methods for genetic testing are capable of resolving deletions and sequence variants, but they mostly fail to provide information on the breakpoints of duplications and balanced structural variants (SV). However, this information may be necessary for their clinical assessment, especially if the carrier’s phenotype is difficult to assess and/or carrier analysis of relatives is not viable. A promising approach to solving such challenging cases arises with access to optical genome mapping (OGM) but has not been systematically explored as of yet.Methods In this retrospective study, we evaluated diagnostic cases from a 1-year period (2023) in which an SV discovery by SOC methods (microarray, karyotyping and whole-exome sequencing) was followed up by OGM, with the objective to unlock clinically relevant information about the SV.Results Seven cases were shown by SOC methods to bear potential pathogenic SVs and were consequently followed up by OGM. Of these, six were solved by the additional use of OGM alone. One case required sequencing after OGM analysis to further specify the SV’s breakpoints. In all seven cases, OGM was crucial for determining the clinical relevance of the detected SV.Conclusion This study describes the use of OGM as a valuable method for characterising duplications and balanced SVs. Often, this additional information does not add to the quality of a clinical report. However, for a subset of patients, these data are critical, especially in the prenatal setting or when no familial analyses are possible.Data are available upon reasonable request. Data are presented in figures, tables and supplemental files. Individual patient data are confidential and cannot be provided. Raw data of whole-exome sequencing, chromosomal microarray and optical genome mapping are available upon reasonable request.