Conclusion of diagnostic odysseys due to inversions disrupting <i>GLI3</i> and <i>FBN1</i>.

ABSTRACT: Many genetic testing methodologies are biased towards picking up structural variants (SVs) that alter copy number. Copy-neutral rearrangements such as inversions are therefore likely to suffer from underascertainment. In this study, manual review prompted by a virtual multidisciplinary team meeting and subsequent bioinformatic prioritisation of data from the 100K Genomes Project was performed across 43 genes linked to well-characterised skeletal disorders. Ten individuals from three independent families were found to harbour diagnostic inversions. In two families, inverted segments of 1.2/14.8 Mb unequivocally disrupted GLI3 and segregated with skeletal features consistent with Greig cephalopolysyndactyly syndrome. For one family, phenotypic blending was due to the opposing breakpoi

SUBMITTER: Pagnamenta AT 

PROVIDER: S-EPMC10176330 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature