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Lookup NU author(s): Dr Miranda Splitt
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023, The Author(s). Börjeson-Forssman-Lehmann syndrome (BFLS) is an X-linked intellectual disability syndrome caused by variants in the PHF6 gene. We ascertained 19 individuals from 15 families with likely pathogenic or pathogenic PHF6 variants (11 males and 8 females). One family had previously been reported. Six variants were novel. We analysed the clinical and genetic findings in our series and compared them with reported BFLS patients. Affected males had classic features of BFLS including intellectual disability, distinctive facies, large ears, gynaecomastia, hypogonadism and truncal obesity. Carrier female relatives of affected males were unaffected or had only mild symptoms. The phenotype of affected females with de novo variants overlapped with the males but included linear skin hyperpigmentation and a higher frequency of dental, retinal and cortical brain anomalies. Complications observed in our series included keloid scarring, digital fibromas, absent vaginal orifice, neuropathy, umbilical hernias, and talipes. Our analysis highlighted sex-specific differences in PHF6 variant types and locations. Affected males often have missense variants or small in-frame deletions while affected females tend to have truncating variants or large deletions/duplications. Missense variants were found in a minority of affected females and clustered in the highly constrained PHD2 domain of PHF6. We propose recommendations for the evaluation and management of BFLS patients. These results further delineate and extend the genetic and phenotypic spectrum of BFLS.
Author(s): Jain V, Foo SH, Chooi S, Moss C, Goodwin R, Berland S, Clarke AJ, Davies SJ, Corrin S, Murch O, Doyle S, Graham GE, Greenhalgh L, Holder SE, Johnson D, Kumar A, Ladda RL, Sell S, Begtrup A, Lynch SA, McCann E, Ostern R, Pottinger C, Splitt M, Fry AE
Publication type: Article
Publication status: Published
Journal: European Journal of Human Genetics
Year: 2023
Pages: Epub ahead of print
Online publication date: 14/09/2023
Acceptance date: 03/08/2023
Date deposited: 27/09/2023
ISSN (print): 1018-4813
ISSN (electronic): 1476-5438
Publisher: Nature Publishing Group
URL: https://doi.org/10.1038/s41431-023-01447-0
DOI: 10.1038/s41431-023-01447-0
PubMed id: 37704779
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