{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T22:27:43Z","timestamp":1783636063519,"version":"3.55.0"},"reference-count":32,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,7,8]],"date-time":"2023-07-08T00:00:00Z","timestamp":1688774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Phenylketonuria (PKU) is an autosomal recessive disease resulting from a deficiency of the enzyme phenylalanine hydroxylase (PAH). Hyperphenylalaninemias (HPA) due to PAH deficiency are accompanied by a wide variety of clinical, biochemical, and molecular features. To identify and characterize pathogenic variants in the PAH gene and establish a correlation between genotype and biochemical phenotype in patients with PKU from state of Par\u00e1 in the North Region of Brazil.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>All 13 exons of the PAH gene from 32 patients (21 PKU and 11 non\u2010PKU HPA) were amplified by PCR and submitted to DNA sequencing (Sanger). Biochemical data were obtained from the patients' medical records.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Molecular analysis identified 17 pathogenic variants and 3 nonpathogenic variants. The most frequent pathogenic variants were IVS10\u201011G&gt;A (7.9%), p. Arg261Gln (7.9%), p. Val388Met (6.3%) and p. Ile65Thr (4.7%). Was observed correlations and inconsistencies between genotype and biochemical phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In PKU patients from state of Par\u00e1, North Region of Brazil, a heterogeneous mutation spectrum was revealed, in which the most frequent mutations are variants commonly observed in other Brazilian studies and in the region of the Iberian Peninsula.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2224","type":"journal-article","created":{"date-parts":[[2023,7,8]],"date-time":"2023-07-08T10:45:22Z","timestamp":1688813122000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Molecular characterization of phenylketonuria patients from the North Region of Brazil: State of Par\u00e1"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7789-9729","authenticated-orcid":false,"given":"Pedro E.","family":"Bonfim\u2010Freitas","sequence":"first","affiliation":[{"name":"Laboratory of Inborn Errors of Metabolism Institute of Biological Sciences, Federal University of Par\u00e1  Bel\u00e9m Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roseani S.","family":"Andrade","sequence":"additional","affiliation":[{"name":"Faculty of Nutrition Institute of Health Sciences, Federal University of Par\u00e1  Bel\u00e9m Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c2ndrea K.","family":"Ribeiro\u2010dos\u2010Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Human and Medical Genetics Institute of Biological Sciences, Federal University of Par\u00e1  Bel\u00e9m Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz C. Santana\u2010da","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Inborn Errors of Metabolism Institute of Biological Sciences, Federal University of Par\u00e1  Bel\u00e9m Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098\u20101004(200102)17:2<122::AID\u2010HUMU4>3.0.CO;2\u2010C"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.08.017"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737159.2014.923760"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(10)60961\u20100"},{"issue":"2","key":"e_1_2_10_6_1","first-page":"337","article-title":"Evidence in Latin America of recurrence of V388M, a phenylketonuria mutation with high in vitro residual activity","volume":"57","author":"Desviat L. R.","year":"1995","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200312"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000472313"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.112.S4.1557"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.1999.2922"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1559"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1086\/301920"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0211048"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2020.06.006"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2018.06.011"},{"issue":"3","key":"e_1_2_10_16_1","first-page":"527","article-title":"The PKU locus in man is on chromosome 12","volume":"36","author":"Lidksy A. S.","year":"1984","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1590\/1414\u2010431X20176709"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.610"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.408"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199105023241802"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050877"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098\u20101004(1999)13:6<503::AID\u2010HUMU12>3.0.CO;2\u2010I"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098\u20101004(1996)8:3<262::AID\u2010HUMU10>3.0.CO;2\u20100"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.35.4.301"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469\u20101809.2008.00476.x"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20526"},{"key":"e_1_2_10_27_1","first-page":"1667","volume-title":"The metabolic and molecular bases of inherited disease","author":"Scriver C. R.","year":"2001"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1096\u20107192(03)00032\u20105"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.114"},{"issue":"1","key":"e_1_2_10_30_1","first-page":"31","article-title":"Phenylketonuria: An inborn error of phenylalanine","volume":"29","author":"Willians A. R.","year":"2008","journal-title":"Clinical Biochemist Reviews"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1141"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10192"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1159\/000312811"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2224","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T08:39:15Z","timestamp":1697099955000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.2224"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,8]]},"references-count":32,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["10.1002\/mgg3.2224"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.2224","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,8]]},"assertion":[{"value":"2022-03-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2224"}}