{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:02:00Z","timestamp":1790737320434,"version":"4.1.0"},"reference-count":22,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      X-linked Alport syndrome (XLAS) is a progressive hereditary nephropathy caused by mutations in the\n                      <jats:italic toggle=\"yes\">COL4A5<\/jats:italic>\n                      gene. Genotype-phenotype correlation in male XLAS is relatively well established; relative to truncating mutations, nontruncating mutations exhibit milder phenotypes. However, transcript comparison between XLAS cases with splicing abnormalities that result in a premature stop codon and those with nontruncating splicing abnormalities has not been reported, mainly because transcript analysis is not routinely conducted in patients with XLAS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We examined transcript expression for all patients with suspected splicing abnormalities who were treated at one hospital between January of 2006 and July of 2017. Additionally, we recruited 46 males from 29 families with splicing abnormalities to examine genotype-phenotype correlation in patients with truncating (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =21, from 14 families) and nontruncating (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =25, from 15 families) mutations at the transcript level.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We detected 41 XLAS families with abnormal splicing patterns and described novel XLAS atypical splicing patterns (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =14) other than exon skipping caused by point mutations in the splice consensus sequence. The median age for developing ESRD was 20 years (95% confidence interval, 14 to 23 years) among patients with truncating mutations and 29 years (95% confidence interval, 25 to 40 years) among patients with nontruncating mutations (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We report unpredictable atypical splicing in the\n                      <jats:italic toggle=\"yes\">COL4A5<\/jats:italic>\n                      gene in male patients with XLAS and reveal that renal prognosis differs significantly for patients with truncating versus nontruncating splicing abnormalities. Our results suggest that splicing modulation should be explored as a therapy for XLAS with truncating mutations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2018030228","type":"journal-article","created":{"date-parts":[[2018,6,29]],"date-time":"2018-06-29T10:07:13Z","timestamp":1530266833000},"page":"2244-2254","source":"Crossref","is-referenced-by-count":66,"title":["Detection of Splicing Abnormalities and Genotype-Phenotype Correlation in X-linked Alport Syndrome"],"prefix":"10.1681","volume":"29","author":[{"given":"Tomoko","family":"Horinouchi","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kandai","family":"Nozu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiko","family":"Yamamura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shogo","family":"Minamikawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Omori","sequence":"additional","affiliation":[{"name":"Clinical and Translational Research Center, Kobe University Hospital, Kobe, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keita","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, 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of Medicine, Kyoto, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Kamei","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenjirou","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Department of Urology, Ehime Prefectural Central Hospital, Ehime, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichiro","family":"Fujinaga","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Saitama Children\u2019s Medical Center, Saitama, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Oka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine Saga University, Saga, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Igarashi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Nippon Medical School, Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinori","family":"Miyazono","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine Kagoshima University, Kagoshima, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7166-4582","authenticated-orcid":false,"given":"Emi","family":"Sawanobori","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Yamanashi, Yamanashi, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rika","family":"Fujimaru","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Osaka General Hospital, Osaka, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Department of Child Health and Welfare (Pediatrics), Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Shima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Wakayama Medical University, Wakayama, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Faculty of Rehabilitation, Kobe Gakuin University, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming Juan","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, 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