{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T13:09:12Z","timestamp":1754399352369,"version":"3.37.3"},"reference-count":22,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,8,29]],"date-time":"2013-08-29T00:00:00Z","timestamp":1377734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004681","name":"Higher Education Commission (HEC) of Pakistan","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004681","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University Research Fund (URF) of Quaid-i-Azam University, Islamabad, Pakistan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Two inherited unconjugated hyperbilirubinemias, Crigler\u2013Najjar syndrome and Gilbert syndrome, arise due to deficiency of UGT1A1 enzyme activity. Crigler\u2013Najjar syndrome type 1 (CN1) lies at the extreme severe end of the spectrum of UGT1A1 activity characterized by complete absence, followed by the less severe Crigler\u2013Najjar syndrome type 2 (CN2). Gilbert syndrome is the mild form having only partial loss of UGT1A1 activity. The present study aimed to identify molecular genetic defects underlying unconjugated hyperbilirubinemias in children from six consanguineous Pakistani families. The patients were clinically diagnosed by exclusion of other unconjugated hyperbilirubinemias. Differential diagnosis of CN1 and CN2 was made on the basis of patient's response to phenobarbitone. The promoter region, coding exons, and adjacent splice sites of the <jats:italic>UGT1A1<\/jats:italic> gene were PCR amplified from genomic DNA of all patients and their families, and were sequenced. DNA sequence analysis identified five different homozygous mutations: two novel missense mutations p.Y230C (proband A) and p.D36N (proband B), a 4\u2010bp insertion c.622\u2013625dupCAGC\/p.Q208QfsX50 (probands C and E), a nonsense mutation p.R341X (proband D), and a TA insertion A(TA)<jats:sub>7<\/jats:sub>TAA in the promoter region (proband F). The present study extends the spectrum of <jats:italic>UGT1A1<\/jats:italic> gene mutations and may be helpful in the diagnosis of Crigler\u2013Najjar syndrome and Gilbert syndrome.<\/jats:p>","DOI":"10.1111\/ahg.12039","type":"journal-article","created":{"date-parts":[[2013,8,30]],"date-time":"2013-08-30T04:31:53Z","timestamp":1377837113000},"page":"482-487","source":"Crossref","is-referenced-by-count":4,"title":["<i>UGT1A1<\/i> Gene Mutations in Pakistani Children Suffering from Inherited Nonhemolytic Unconjugated Hyperbilirubinemias"],"prefix":"10.1111","volume":"77","author":[{"given":"Suliman","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Biotechnology Quaid\u2010i\u2010Azam University  Islamabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Irfan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Quaid\u2010i\u2010Azam University  Islamabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gulab","family":"Sher","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Quaid\u2010i\u2010Azam University  Islamabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bibi","family":"Zubaida","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Quaid\u2010i\u2010Azam University  Islamabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad Arshad","family":"Alvi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology The Children's Hospital &amp; The Institute of Child Health  Lahore Pakistan"},{"name":"King Faisal Specialist Hospital &amp; Research Centre  Jeddah Kingdom of Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masoom","family":"Yasinzai","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Quaid\u2010i\u2010Azam University  Islamabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Naeem","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Quaid\u2010i\u2010Azam University  Islamabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,8,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI104682"},{"key":"e_1_2_8_3_1","first-page":"66","article-title":"Chronic nonhemolytic unconjugated hyperbilirubinemia with glucuronyl transferase deficiency: Evidence for genetic heterogeneity","volume":"81","author":"Arias I. 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Disease: Crigler\u2010Najjar syndrome 1","volume":"127","author":"Kohli S.","year":"2010","journal-title":"Hum Genet"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M206136200"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703107200"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2009.11.013"},{"key":"e_1_2_8_19_1","first-page":"722","article-title":"Co\u2010segregation of intragenic markers with a novel mutation that causes Crigler\u2010Najjar syndrome type 1: Implication in carrier detection and prenatal diagnosis","volume":"53","author":"Moghrabi N.","year":"1993","journal-title":"Am J Hum Genet"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2009.07.025"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)50724-4"},{"key":"e_1_2_8_22_1","first-page":"150","article-title":"Molecular pathology of Crigler\u2013Najjar type 1 and II and Gilbert's syndromes","volume":"84","author":"Sampietro M.","year":"1999","journal-title":"Hematol J"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117604"}],"container-title":["Annals of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fahg.12039","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fahg.12039","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ahg.12039","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T08:17:33Z","timestamp":1696493853000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ahg.12039"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,8,29]]},"references-count":22,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2013,11]]}},"alternative-id":["10.1111\/ahg.12039"],"URL":"https:\/\/doi.org\/10.1111\/ahg.12039","archive":["Portico"],"relation":{},"ISSN":["0003-4800","1469-1809"],"issn-type":[{"type":"print","value":"0003-4800"},{"type":"electronic","value":"1469-1809"}],"subject":[],"published":{"date-parts":[[2013,8,29]]}}}