{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T18:19:04Z","timestamp":1772648344134,"version":"3.50.1"},"reference-count":16,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T00:00:00Z","timestamp":1692835200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Thirteen affected individuals of six generations of a single kindred presented with epiphora evident from infancy. Physical exam and Schirmer test revealed variable expression of tear deficiency, congenital punctal atresia, and dry mouth with multiple caries, without concomitant abnormalities of the ears or digits, commensurate with a diagnosis of aplasia of the lacrimal and salivary glands (ALSG). Reconstruction of the upper lacrimal drainage system was performed in some of the affected individuals. Genetic analysis, testing six affected individuals and three non\u2010affected family members, identified a single novel heterozygous splice\u2010site variant, c.429\u2009+\u20091, G\u2009&gt;\u2009T in fibroblast growth factor 10 (<jats:italic>FGF10<\/jats:italic>) (NM_004465.1), segregating throughout the family as expected for dominant heredity. RT\u2010PCR assays of HEK\u2010293 cells transfected with wild type or mutant <jats:italic>FGF10<\/jats:italic> demonstrated that the variant causes skipping of Exon 2. Notably, individuals sharing the same variant exhibited phenotypic variability, with unilateral or bilateral epiphora, as well as variable expression of dry mouth and caries. Moreover, one of the variant carriers had no ALSG\u2010related clinical findings, demonstrating incomplete penetrance. While coding mutations in <jats:italic>FGF10<\/jats:italic> are known to cause malformations in the nasolacrimal system, this is the second <jats:italic>FGF10<\/jats:italic> splice\u2010site variant and the first donor\u2010site variant reported to cause ALSG. Thus, our study of a unique large kindred with multiple affected individuals heterozygous for the same <jats:italic>FGF10<\/jats:italic> variant highlights intronic splice\u2010site mutations and phenotypic variability\/partial penetrance in ALSG.<\/jats:p>","DOI":"10.1002\/ajmg.a.63359","type":"journal-article","created":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T11:21:14Z","timestamp":1692876074000},"page":"2768-2774","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Partial penetrance and phenotypic variability of aplasia of lacrimal and salivary glands caused by a novel <scp><i>FGF10<\/i><\/scp> donor splice\u2010site mutation"],"prefix":"10.1002","volume":"191","author":[{"given":"Ofek","family":"Freund","sequence":"first","affiliation":[{"name":"The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev  Beer\u2010Sheva Israel"},{"name":"The Shraga Segal Department 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Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matan M.","family":"Jean","sequence":"additional","affiliation":[{"name":"The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev  Beer\u2010Sheva Israel"},{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences Ben\u2010Gurion University of the Negev  Beer\u2010Sheva Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amit","family":"Safran","sequence":"additional","affiliation":[{"name":"The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev  Beer\u2010Sheva Israel"},{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences Ben\u2010Gurion University of the Negev  Beer\u2010Sheva 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