RT Journal Article
SR Electronic
T1 Retrospective study on the utility of optical genome mapping as a follow-up method in genetic diagnostics
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 89
OP 96
DO 10.1136/jmg-2024-110265
VO 62
IS 2
A1 Dremsek, Paul
A1 Schachner, Anna
A1 Reischer, Theresa
A1 Krampl-Bettelheim, Elisabeth
A1 Bettelheim, Dieter
A1 Vrabel, Sybille
A1 Delissen, Zoja
A1 Pfeifer, Mateja
A1 Weil, Beatrix
A1 Bajtela, Robert
A1 Hengstschläger, Markus
A1 Laccone, Franco
A1 Neesen, Jürgen
YR 2025
UL http://jmg.bmj.com/content/62/2/89.abstract
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.