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Germline heterozygous mutations in <jats:italic>POFUT1<\/jats:italic> gene cause Dowling\u2013Degos disease (DDD), a skin disease that features flexural reticulated hyperpigmentation and follicular\u2010based lesions. <jats:italic>POFUT1<\/jats:italic> mosaicism has not been described to date. Here, we describe a 9\u2010year\u2010old female with segmental hyper\u2010 and hypopigmented patches with overlying eczematous plaques and follicular papules. Employing paired whole exome sequencing of saliva and keratinocytes isolated from affected skin, we found a novel germline heterozygous <jats:italic>POFUT1<\/jats:italic> deletion causing frameshift and premature codon termination and somatic copy\u2010neutral loss of heterozygosity on chromosome 20 encompassing <jats:italic>POFUT1<\/jats:italic>. Expression levels of <jats:italic>POFUT1<\/jats:italic> as well as other key regulators of the notch signaling pathway\u2014<jats:italic>NOTCH1<\/jats:italic>, <jats:italic>NOTCH2<\/jats:italic>, and <jats:italic>HES1<\/jats:italic>\u2014were reduced in affected keratinocytes compared with normal keratinocytes. Our findings provide the first evidence of <jats:italic>POFUT1<\/jats:italic> postzygotic mutation and a phenotypic expansion of <jats:italic>POFUT1<\/jats:italic> loss of function mutations. We show that a recessive loss of function mutation in <jats:italic>POFUT1<\/jats:italic> produces a distinct clinical presentation with features (e.g., dermatitis) that are absent in the generalized form of DDD. This study demonstrates how analysis of mosaic disorders can reveal unexpected phenotypes for known genes.<\/jats:p>","DOI":"10.1002\/ajmg.a.61362","type":"journal-article","created":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T05:00:26Z","timestamp":1569906026000},"page":"2469-2473","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Phenotypic expansion of <i>POFUT1<\/i> loss of function mutations in a disorder featuring segmental dyspigmentation with eczematous and folliculo\u2010centric lesions"],"prefix":"10.1002","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5149-5777","authenticated-orcid":false,"given":"Lihi","family":"Atzmony","sequence":"first","affiliation":[{"name":"Department of Dermatology Yale University School of Medicine  New Haven Connecticut"},{"name":"Department of Genetics Yale University School of Medicine  New Haven Connecticut"},{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2176-4822","authenticated-orcid":false,"given":"Theodore D.","family":"Zaki","sequence":"additional","affiliation":[{"name":"Department of Dermatology Yale University School of Medicine  New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Antaya","sequence":"additional","affiliation":[{"name":"Department of Dermatology Yale University School of Medicine  New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1010-6354","authenticated-orcid":false,"given":"Keith A.","family":"Choate","sequence":"additional","affiliation":[{"name":"Department of Dermatology Yale University School of Medicine  New Haven Connecticut"},{"name":"Department of Genetics Yale University School of Medicine  New Haven Connecticut"},{"name":"Department of Pathology Yale University School of Medicine  New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,9,30]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"176","article-title":"Effectiveness of topical adapalene in Dowling\u2010Degos disease","volume":"198","author":"Altomare G.","year":"1999","journal-title":"Diamond and Related 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