{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:09:44Z","timestamp":1787022584112,"version":"build-2736575974"},"reference-count":30,"publisher":"Walter de Gruyter GmbH","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_jpem-2022-0047_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      The aim of our study was to define the genotype\u2013phenotype correlations of mutations in the\n                      <jats:italic>PAH<\/jats:italic>\n                      gene among the Turkey\u2019s Central Anatolian region.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2022-0047_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Demographic characteristics of 108 patients with hyperphenylalaninemia (HPA) and 94 patients whose diagnosis was confirmed by\n                      <jats:italic>PAH<\/jats:italic>\n                      gene analysis (Sanger DNA Sequence Analysis and Next-Generation Sequencing) were determined retrospectively. Blood phenylalanine levels were analyzed using the high-performance liquid chromatography method.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2022-0047_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Mild HPA-not-requiring-treatment (NT) was found in 50.9% of the patients, and a classical phenylketonuria (PKU) phenotype was found in 25.9%. Forty-seven types of variants were identified. The predominant variants were p.Ala403Val (9.9%), p.Ala300Ser (9.4%), and c.1066-11G&gt;A (splicing) (9.4%). Missense mutations accounted for 68% of mutations and attenuated the clinical impact; splice variations were found in 14.8% of cases with severe features. The p.Thr380Met\u00a0allele was specific to the mild HPA-NT group. The c.1066-11G&gt;A (splicing) allele was associated with classical PKU, whereas the p.Arg408Trp allele was linked to severe symptoms. Three variations of unknown clinical significance were discovered: c.706+4A&gt;T (splicing), c.843-5T&gt;C (splicing), and p.Thr323=. Of these variants, the patient who was homozygous for the c.843-5T&gt;C (splicing) allele related to the classical PKU phenotype. 70% of the patients who underwent tetrahydrobiopterin (BH4) test were responsive. Phenotypes that responded to BH4 treatment were mostly mild phenotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2022-0047_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>PAH<\/jats:italic>\n                      genotype is the main factor that determines the phenotype of PKU. Establishing the relationship between the identified genetic mutations and phenotypic characteristics will provide very important data for each patient in terms of the specific management style.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/jpem-2022-0047","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T21:25:33Z","timestamp":1648675533000},"page":"639-647","source":"Crossref","is-referenced-by-count":9,"title":["Spectrum of\n                    <i>PAH<\/i>\n                    gene mutations and genotype\u2013phenotype correlation in patients with phenylalanine hydroxylase deficiency from Turkey"],"prefix":"10.1515","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4309-2331","authenticated-orcid":false,"given":"M\u00fcge","family":"\u00c7\u0131nar","sequence":"first","affiliation":[{"name":"Pediatrics , Boz\u00fcy\u00fck State Hospital , Bilecik , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6769-667X","authenticated-orcid":false,"given":"Gonca","family":"K\u0131l\u0131\u00e7 Y\u0131ld\u0131r\u0131m","sequence":"additional","affiliation":[{"name":"Department of Paediatrics , Eskisehir Osmangazi University Faculty of Medicine, Division of Child Nutrition and Metabolism , Eskisehir , Turkey"},{"name":"Eskisehir Osmangazi University Faculty of Medicine , Meselik Campuse , Odunpazari , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2595-3919","authenticated-orcid":false,"given":"Sinem","family":"Kocagil","sequence":"additional","affiliation":[{"name":"Eskisehir Osmangazi University Faculty of Medicine , Meselik Campuse , Odunpazari , Turkey"},{"name":"Department of Genetics and Genomics Medicine , Eskisehir Osmangazi University Faculty of Medicine , Eskisehir , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5593-4164","authenticated-orcid":false,"given":"O\u011fuz","family":"\u00c7ilingir","sequence":"additional","affiliation":[{"name":"Eskisehir Osmangazi University Faculty of Medicine , Meselik Campuse , Odunpazari , Turkey"},{"name":"Department of Genetics and Genomics Medicine , Eskisehir Osmangazi University Faculty of Medicine , Eskisehir , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2022,3,30]]},"reference":[{"key":"2023033121124496427_j_jpem-2022-0047_ref_001","doi-asserted-by":"crossref","unstructured":"Koppes, EA, Redel, BK, Johnson, MA, Skvorak, KJ, Ghaloul-Gonzalez, L, Yates, ME, et al.. 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