{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:11:58Z","timestamp":1760145118865,"version":"build-2065373602"},"reference-count":15,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T00:00:00Z","timestamp":1718582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>The diagnosis of hereditary skin tumors is difficult for \u201cold\u201d diagnostic tools such as immunohistochemistry. Whole-exome sequencing analysis as a \u201cnew\u201d diagnostic tool enables us to make a final diagnosis in spite of unknown hereditary diseases in the past. Hereditary leiomyomatosis and renal cell cancer are autosomal dominant hereditary cancer syndromes characterized by uterine myomas, cutaneous leiomyomas, and aggressive renal cell cancer. The syndrome is associated with pathogenic germline variants in the fumarate hydratase gene. Herein, we demonstrate a pathogenic germline variant of the fumarate hydratase gene in a 60-year-old woman with multiple cutaneous leiomyomas, leading to the diagnosis of hereditary leiomyomatosis and renal cell cancer. Whole-exome sequencing analysis using genomic DNA extracted from peripheral blood leukocytes revealed one germline variant in the FH gene on chromosome 1 (c.290G&gt;A, p.Gly97Asp). She received total hysterectomy due to uterine myoma, which strongly supported the diagnosis. No tumor was detected in her kidney by computed tomography and ultrasound examination. Genetic examination for the mutation of the fumarate hydratase gene is important in order to reach the correct diagnosis and to detect renal cancer at its early stage.<\/jats:p>","DOI":"10.3390\/diagnostics14121279","type":"journal-article","created":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T08:48:31Z","timestamp":1718614111000},"page":"1279","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Whole-Exome Sequencing Revealed a Pathogenic Germline Variant in the Fumarate Hydratase Gene, Leading to the Diagnosis of Hereditary Leiomyomatosis and Renal Cell Cancer"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8334-5165","authenticated-orcid":false,"given":"Akari","family":"Nagashima","sequence":"first","affiliation":[{"name":"Department of Dermatology, International University of Health and Welfare, Narita 286-8520, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sohshi","family":"Morimura","sequence":"additional","affiliation":[{"name":"Department of Dermatology, International University of Health and Welfare, Narita 286-8520, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihisa","family":"Hamada","sequence":"additional","affiliation":[{"name":"Department of Dermatology, International University of Health and Welfare, Narita 286-8520, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4250-1204","authenticated-orcid":false,"given":"Takayuki","family":"Shiomi","sequence":"additional","affiliation":[{"name":"Department of Pathology, International University of Health and Welfare, Narita 286-8520, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ichiro","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Pathology, International University of Health and Welfare, Narita 286-8520, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoko","family":"Sato","sequence":"additional","affiliation":[{"name":"Center for Genomic Diagnosis, International University of Health and Welfare, Narita 286-8520, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junko","family":"Nomoto","sequence":"additional","affiliation":[{"name":"Center for Genomic Diagnosis, International University of Health and Welfare, Narita 286-8520, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Center for Genomic Diagnosis, International University of Health and Welfare, Narita 286-8520, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shoji","family":"Tsuji","sequence":"additional","affiliation":[{"name":"Center for Genomic Diagnosis, International University of Health and Welfare, Narita 286-8520, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1618-329X","authenticated-orcid":false,"given":"Makoto","family":"Sugaya","sequence":"additional","affiliation":[{"name":"Department of Dermatology, International University of Health and Welfare, Narita 286-8520, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,17]]},"reference":[{"key":"ref_1","first-page":"48","article-title":"Hereditary multiple leiomyoma of the skin","volume":"10","author":"Kloepfer","year":"1958","journal-title":"Am. 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Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1080\/14728222.2020.1804862","article-title":"Fumarate hydratase as a therapeutic target in renal cancer","volume":"24","author":"Kancherla","year":"2020","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/j.molcel.2022.01.029","article-title":"Fumarate inhibits PTEN to promote tumorigenesis and therapeutic resistance of type2 papillary renal cell carcinoma","volume":"82","author":"Ge","year":"2022","journal-title":"Mol. 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