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. 2022 Nov;43(11):1659-1665.
doi: 10.1002/humu.24467. Epub 2022 Oct 2.

Next-generation phenotyping contributing to the identification of a 4.7 kb deletion in KANSL1 causing Koolen-de Vries syndrome

Fabian Brand  1 , Aswinkumar Vijayananth  1 , Tzung-Chien Hsieh  1 , Axel Schmidt  2 , Sophia Peters  2 , Elisabeth Mangold  2 , Kirsten Cremer  2 , Tim Bender  3 , Sugirthan Sivalingam  4 , Hela Hundertmark  2 , Alexej Knaus  1 , Hartmut Engels  2 , Peter M Krawitz  1 , Claudia Perne  2
Affiliations

Next-generation phenotyping contributing to the identification of a 4.7 kb deletion in KANSL1 causing Koolen-de Vries syndrome

Fabian Brand et al. Hum Mutat. 2022 Nov.

Abstract

Next-generation phenotyping (NGP) is an 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 8 and 15 and enrolled in NGP diagnostics on the latter occasion. The girl had clinical features associated with Koolen-de Vries syndrome (KdVS) and a suggestive facial gestalt. However, chromosomal microarray (CMA), Sanger sequencing, multiplex ligation-dependent probe analysis (MLPA), and trio exome sequencing remained inconclusive. Based on the highly indicative gestalt score for KdVS, the decision was made to perform genome sequencing to also evaluate noncoding variants. This analysis revealed a 4.7 kb de novo deletion partially affecting intron 6 and exon 7 of the KANSL1 gene. This 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.

Keywords: Koolen-de Vries syndrome; WGS; next-generation phenotyping; structural variant.

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REFERENCES

    1. Chen, X., Schulz-Trieglaff, O., Shaw, R., Barnes, B., Schlesinger, F., Kallberg, M., Cox, A. J., Kruglyak, S., & Saunders, C. T. (2016). Manta: Rapid detection of structural variants and indels for germline and cancer sequencing applications. Bioinformatics, 32(8), 1220-1222. https://doi.org/10.1093/bioinformatics/btv710
    1. Cooper, G. M., Coe, B. P., Girirajan, S., Rosenfeld, J. A., Vu, T. H., Baker, C., Williams, C., Stalker, H., Hamid, R., Hannig, V., Abdel-Hamid, H., Bader, P., McCracken, E., Niyazov, D., Leppig, K., Thiese, H., Hummel, M., Alexander, N., Gorski, J., … Eichler, E. E. (2011). A copy number variation morbidity map of developmental delay. Nature Genetics, 43(9), 838-846. https://doi.org/10.1038/ng.909
    1. Dingemans, A. J. M., Stremmelaar, D. E., van der Donk, R., Vissers, L., Koolen, D. A., Rump, P., Hehir-Kwa, J. Y., & de Vries, B. B. A. (2021). Quantitative facial phenotyping for koolen-de vries and 22q11.2 deletion syndrome. European Journal of Human Genetics, 29(9), 1418-1423. https://doi.org/10.1038/s41431-021-00824-x
    1. van der Donk, R., Jansen, S., Schuurs-Hoeijmakers, J. H. M., Koolen, D. A., Goltstein, L., Hoischen, A., Brunner, H. G., Kemmeren, P., Nellaker, C., Vissers, L., de Vries, B. B. A., & Hehir-Kwa, J. Y. (2019). Next-generation phenotyping using computer vision algorithms in rare genomic neurodevelopmental disorders. Genetics in Medicine, 21(8), 1719-1725. https://doi.org/10.1038/s41436-018-0404-y
    1. Dubourg, C., Sanlaville, D., Doco-Fenzy, M., Le Caignec, C., Missirian, C., Jaillard, S., Schluth-Bolard, C., Landais, E., Boute, O., Philip, N., Toutain, A., David, A., Edery, P., Moncla, A., Martin-Coignard, D., Vincent-Delorme, C., Mortemousque, I., Duban-Bedu, B., Drunat, S., … Andrieux, J. (2011). Clinical and molecular characterization of 17q21.31 microdeletion syndrome in 14 French patients with mental retardation. European Journal of Medical Genetics, 54(2), 144-151. https://doi.org/10.1016/j.ejmg.2010.11.003

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