{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:54:03Z","timestamp":1790394843091,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,8,31]],"date-time":"2016-08-31T00:00:00Z","timestamp":1472601600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005378","name":"Hacettepe \u00dcniversitesi","doi-asserted-by":"publisher","award":["946"],"award-info":[{"award-number":["946"]}],"id":[{"id":"10.13039\/501100005378","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatrics International"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>In single gene disorders, patients with the same genotype may have variations in severity. One of the main factors affecting disease severity is modifier genes. Spinal muscular atrophy (<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content>) is an autosomal recessive neuromuscular disorder caused by degeneration of alpha motor neurons. <jats:italic>Plastin 3<\/jats:italic> (<jats:italic><jats:styled-content style=\"fixed-case\">PLS<\/jats:styled-content>3<\/jats:italic>) is a phenotypic modifier of <jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content>, and <jats:italic>neuritin 1<\/jats:italic> (<jats:italic><jats:styled-content style=\"fixed-case\">NRN<\/jats:styled-content>1<\/jats:italic>) has also been suggested as a possible modifier gene. The aim of the present study was therefore to analyze <jats:italic><jats:styled-content style=\"fixed-case\">PLS<\/jats:styled-content>3<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">NRN<\/jats:styled-content>1<\/jats:italic> expression in <jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> siblings in four families.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study group consisted of four <jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> families with seven with discordant phenotype and two affected siblings. Total <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> was isolated from whole blood. <jats:italic><jats:styled-content style=\"fixed-case\">PLS<\/jats:styled-content>3<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">NRN<\/jats:styled-content>1<\/jats:italic> expression was analyzed on quantitative real\u2010time polymerase chain reaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In family 1 only <jats:italic><jats:styled-content style=\"fixed-case\">NRN<\/jats:styled-content>1<\/jats:italic> expression was increased in the mildly affected sister. In family 2 only <jats:italic><jats:styled-content style=\"fixed-case\">PLS<\/jats:styled-content>3<\/jats:italic> had a modifier effect. Family 3, which had type <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content> siblings with identical clinical phenotypes, had similar <jats:italic><jats:styled-content style=\"fixed-case\">PLS<\/jats:styled-content>3<\/jats:italic> expression between the siblings but no <jats:italic><jats:styled-content style=\"fixed-case\">NRN<\/jats:styled-content>1<\/jats:italic> expression. In family 4, neither <jats:italic><jats:styled-content style=\"fixed-case\">PLS<\/jats:styled-content>3<\/jats:italic> nor <jats:italic><jats:styled-content style=\"fixed-case\">NRN<\/jats:styled-content>1<\/jats:italic> had any correlation with severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>On analysis of the expression of <jats:italic><jats:styled-content style=\"fixed-case\">NRN<\/jats:styled-content>1<\/jats:italic> in <jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> patients for the first time, <jats:italic><jats:styled-content style=\"fixed-case\">NRN<\/jats:styled-content>1<\/jats:italic> could be a potential modifier gene. <jats:italic><jats:styled-content style=\"fixed-case\">PLS<\/jats:styled-content>3<\/jats:italic> expression does not always modify <jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> phenotype. In patients with no modifier effect of known genes, genome sequencing and transcriptome analysis are promising for the identification of novel modifiers and understanding of <jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> pathophysiology.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ped.13052","type":"journal-article","created":{"date-parts":[[2016,6,9]],"date-time":"2016-06-09T07:43:36Z","timestamp":1465458216000},"page":"53-56","source":"Crossref","is-referenced-by-count":20,"title":["Transcript levels of <i>plastin 3<\/i> and <i>neuritin 1<\/i> modifier genes in spinal muscular atrophy siblings"],"prefix":"10.1111","volume":"59","author":[{"given":"\u0130nci Hande","family":"Yener","sequence":"first","affiliation":[{"name":"Department of Medical Biology Faculty of Medicine Hacettepe University Sihhiye Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haluk","family":"Topaloglu","sequence":"additional","affiliation":[{"name":"Department of 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