{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T09:29:54Z","timestamp":1760866194095,"version":"3.41.2"},"reference-count":20,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,8,3]],"date-time":"2019-08-03T00:00:00Z","timestamp":1564790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81530023","81600405","81770662","81800589","81830020"],"award-info":[{"award-number":["81530023","81600405","81770662","81800589","81830020"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Lowe syndrome is a rare X\u2011linked syndrome that is characterized by involvement of the eyes, central nervous system, and kidneys. The aim of the present study was to determine the molecular basis of four patients with congenital cataract, infantile congenital hypotonia, and proximal renal tubular defect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Four children who met the clinical manifestations of Lowe syndrome were enrolled in this study. Patients\u2019 clinical information on eyes, central nervous system, kidneys, and family histories, etc., were reviewed and analyzed. After obtaining informed consent, we performed a mutation analysis of <jats:italic>OCRL<\/jats:italic> gene using direct sequencing. Because of failure of PCR amplification, low coverage shortread whole genome sequencing (CNVseq) analysis was performed on one proband. Real\u2010time PCR was subsequently performed to confirm the CNV that was detected from the CNVseq results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified three <jats:italic>OCRL<\/jats:italic> allelic variants, including two novel missense mutations (c.1423C&gt;T\/p.Pro475Ser, c.1502T&gt;G\/p.Ile501Ser) and one recurrent nonsense mutation (c.2464C&gt;T\/p.Arg822Ter). Various bioinformatic tools revealed scores associated with potential pathogenic effects for the two missense variants, and protein alignments revealed that both variants affected an amino acid highly conserved among species. Since deletion of the entire gene was suspected in a patient, CNVseq was used, identifying an interstitial deletion to approximately 190\u00a0kb, encompassing <jats:italic>OCRL<\/jats:italic>, and <jats:italic>SMARCA1<\/jats:italic> gene. Moreover, the hemizygous CNV was confirmed by qPCR. Reviewing another case reported in the literature, we found that the deletion of OCRL and nearby genes may contribute to a more severe phenotype and premature death.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This is the first report of an interstitial deletion encompassing <jats:italic>OCRL<\/jats:italic> and <jats:italic>SMARCA1<\/jats:italic> gene in Lowe syndrome. Our results expand the spectrum of mutations of the <jats:italic>OCRL<\/jats:italic> gene in Chinese population. Moreover, whole\u2010genome sequencing presents a comprehensive and reliable approach for detecting genomic copy number variation in patients or carriers in the family with rare inherited disorders.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.876","type":"journal-article","created":{"date-parts":[[2019,8,3]],"date-time":"2019-08-03T07:38:18Z","timestamp":1564817898000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Whole\u2010genome sequencing revealed an interstitial deletion encompassing <i>OCRL<\/i> and <i>SMARCA1<\/i> gene in a patient with Lowe syndrome"],"prefix":"10.1002","volume":"7","author":[{"given":"Bixia","family":"Zheng","sequence":"first","affiliation":[{"name":"Nanjing Key Laboratory of Pediatrics Children\u2019s Hospital of Nanjing Medical University Nanjing 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"SongMing","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Nephrology Children\u2019s Hospital of Nanjing Medical University Nanjing China"},{"name":"Jiangsu Key Laboratory of Pediatrics Nanjing Medical University Nanjing 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