{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T12:42:13Z","timestamp":1776688933089,"version":"3.51.2"},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T00:00:00Z","timestamp":1686528000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Knudson's \u201ctwo hit\u201d hypothesis, mostly associated with cancer, relates to a primary heterozygous germline mutation complemented by a somatic mutation in the second allele. When the somatic \u201csecond hit\u201d is a deletion mutation, the heterozygosity due to the first hit is lost (\u201closs of heterozygosity\u201d). As the rate of germline mutations is almost two orders of magnitude lower than that of somatic mutations, de\u2010novo germline mutations causing autosomal recessive diseases in carriers of inherited heterozygous mutations are not common. We delineate a case of high myopia presenting at infancy with mild diminution of retinal responses. Exome sequencing identified a paternally inherited apparently homozygous missense mutation in <jats:italic>RBP3<\/jats:italic>. Chromosomal microarrays delineated a de\u2010novo germline heterozygous deletion encompassing <jats:italic>RBP3<\/jats:italic>, verified through revision of WES data. Thus, we demonstrate an inherited <jats:italic>RBP3<\/jats:italic> missense mutation complemented by a de\u2010novo germline <jats:italic>RBP3<\/jats:italic> deletion, causing loss of heterozygosity of the inherited mutation. We describe a novel <jats:italic>RBP3<\/jats:italic> missense mutation, report the first isolated <jats:italic>RBP3<\/jats:italic> deletion, and demonstrate infantile high myopia as an initial presentation of <jats:italic>RBP3<\/jats:italic> disease. Notably, we highlight de\u2010novo germline deletion mutations causing \u201closs of heterozygosity\u201d of inherited heterozygous mutations, culminating in autosomal recessive diseases, and discuss the scarce literature.<\/jats:p>","DOI":"10.1111\/cge.14384","type":"journal-article","created":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T01:50:32Z","timestamp":1686621032000},"page":"571-576","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["De\u2010novo \u201cgermline second hit\u201d loss\u2010of\u2010heterozygosity <i>RBP3<\/i> deletion mutation causing recessive high myopia"],"prefix":"10.1111","volume":"104","author":[{"given":"Maya","family":"Gombosh","sequence":"first","affiliation":[{"name":"The Morris Kahn Laboratory of Human Genetics, Faculty of Health Sciences Ben\u2010Gurion University  Beer\u2010Sheva 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