{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:37:15Z","timestamp":1790501835786,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T00:00:00Z","timestamp":1655164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["ZW184\/3\u20101"],"award-info":[{"award-number":["ZW184\/3\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>While inherited hemizygous variants in <jats:italic>PHF6<\/jats:italic> cause X\u2010linked recessive Borjeson\u2010Forssman\u2010Lehmann syndrome (BFLS) in males, de novo heterozygous variants in females are associated with an overlapping but distinct phenotype, including moderate to severe intellectual disability, characteristic facial dysmorphism, dental, finger and toe anomalies, and linear skin pigmentation. By personal communication with colleagues, we assembled 11 additional females with BFLS due to variants in <jats:italic>PHF6<\/jats:italic>. We confirm the distinct phenotype to include variable intellectual disability, recognizable facial dysmorphism and other anomalies. We observed skewed X\u2010inactivation in blood and streaky skin pigmentation compatible with functional mosaicism. Variants occurred de novo in 10 individuals, of whom one was only mildly affected and transmitted it to her more severely affected daughter. The mutational spectrum comprises a two\u2010exon deletion, five truncating, one splice\u2010site and three missense variants, the latter all located in the PHD2 domain and predicted to severely destabilize the domain structure. This observation supports the hypothesis of more severe variants in females contributing to gender\u2010specific phenotypes in addition to or in combination with effects of X\u2010inactivation and functional mosaicism. Therefore, our findings further delineate the clinical and mutational spectrum of female BFLS and provide further insights into possible genotype\u2013phenotype correlations between females and males.<\/jats:p>","DOI":"10.1111\/cge.14173","type":"journal-article","created":{"date-parts":[[2022,6,4]],"date-time":"2022-06-04T04:19:20Z","timestamp":1654316360000},"page":"182-190","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Further characterization of <scp>Borjeson\u2010Forssman\u2010Lehmann<\/scp> syndrome in females due to de novo variants in <scp><i>PHF6<\/i><\/scp>"],"prefix":"10.1111","volume":"102","author":[{"given":"C\u00e9line B.","family":"Gerber","sequence":"first","affiliation":[{"name":"Department of Human Genetics Inselspital, Bern University Hospital, University of Bern  Bern 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