loading page

Next-generation phenotyping contributing to the identification of a non-coding deletion in KANSL1 causing Koolen-de Vries syndrome
  • Peter Krawitz,
  • Fabian Brand,
  • Claudia Perne
Peter Krawitz
University of Bonn

Corresponding Author:[email protected]

Author Profile
Fabian Brand
University of Bonn
Author Profile
Claudia Perne
University of Bonn
Author Profile


Next-generation phenotyping (NGP) is the application of advanced methods of computer vision on medical imaging data such as portrait photos of individuals with rare disorders. NGP on portraits results in gestalt scores that can be used for the selection of appropriate genetic tests, and for the interpretation of the molecular data. Here, we report on an exceptional case of a young girl that was presented at the age of eight and fifteen and enrolled in NGP diagnostics at the latter occasion. The girl had clinical features associated with Koolen-de Vries syndrome and a suggestive facial gestalt. However, chromosomal micro array (CMA), Sanger sequencing, multiplex ligation-dependent probe analysis (MLPA), and trio exome sequencing remained inconclusive. Based on the highly indicative gestalt score for Koolen-de Vries, the decision was made to perform genome sequencing to also evaluate non-coding variants. This analysis revealed a 4.7 kb deletion at the end of intron 6 of the KANSL1 gene, which is the smallest reported structural variant to date for this phenotype. The case illustrates how NGP can be integrated into the iterative diagnostic process of test selection and interpretation of sequencing results.
18 Apr 2022Submitted to Human Mutation
19 Apr 2022Submission Checks Completed
19 Apr 2022Assigned to Editor
22 Apr 2022Reviewer(s) Assigned
26 May 2022Review(s) Completed, Editorial Evaluation Pending
01 Jun 2022Editorial Decision: Revise Major
05 Jul 20221st Revision Received
18 Jul 2022Assigned to Editor
18 Jul 2022Submission Checks Completed
20 Jul 2022Reviewer(s) Assigned
05 Aug 2022Review(s) Completed, Editorial Evaluation Pending
05 Aug 2022Editorial Decision: Revise Minor
15 Aug 20222nd Revision Received
08 Sep 2022Assigned to Editor
08 Sep 2022Submission Checks Completed
08 Sep 2022Review(s) Completed, Editorial Evaluation Pending
08 Sep 2022Editorial Decision: Accept