{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:09:38Z","timestamp":1772168978919,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/f1000research.2-32.v1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2013,3,20]],"date-time":"2013-03-20T00:00:00Z","timestamp":1363737600000}}],"reference-count":12,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2013,3,20]],"date-time":"2013-03-20T00:00:00Z","timestamp":1363737600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Background<\/ns4:bold>\n                    <ns4:bold>:<\/ns4:bold>\n                    Neonatal cholestasis is a common presentation of childhood liver diseases and can be a feature of various conditions including disorders of bile acid biogenesis and transport, various inborn errors of metabolism and perinatal infections. Some inherited metabolic diseases can be easily screened using biochemical assays, however many can only be accurately diagnosed by DNA sequencing. Fluorescent capillary Sanger sequencing (FS) is the gold standard method used by clinical laboratories for genetic diagnosis of many inherited conditions; however, it does have limitations. Recently microarray resequencing (MR) has been introduced into research and clinical practice as an alternative method for genetic diagnosis of heterogeneous conditions. In this report we compared the accuracy of mutation detection for MR with FS in a group of patients with \u2018low-normal\u2019 gamma glutamyl transpeptidase (gGT) cholestasis without known molecular diagnoses.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods<\/ns4:bold>\n                    <ns4:bold>:<\/ns4:bold>\n                    29 patient DNA samples were tested for mutations in the\n                    <ns4:italic>ATP8B1<\/ns4:italic>\n                    and\n                    <ns4:italic>ABCB11<\/ns4:italic>\n                    genes using both FS and MR. Other known causes of \u201clow gGT cholestasis\u201d such as ARC syndrome and bile acid biosynthesis disorders were excluded.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Results<\/ns4:bold>\n                    <ns4:bold>:<\/ns4:bold>\n                    Mutations were identified in 13\/29 samples. In 3\/29 samples FS and MR gave discordant results: MR had a false positive rate of 3.4% and a false negative rate of 7%.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusions<\/ns4:bold>\n                    <ns4:bold>:<\/ns4:bold>\n                    The major advantage of MR over FS is that multiple genes can be screened in one experiment, allowing rapid and cost-effective diagnoses.\u00a0 However, we have demonstrated that MR technology is limited in sensitivity. We therefore recommend that MR be used as an initial evaluation, with FS deployed when genetic and clinical or histopathological findings are discordant.\n                  <\/ns4:p>","DOI":"10.12688\/f1000research.2-32.v2","type":"journal-article","created":{"date-parts":[[2013,3,20]],"date-time":"2013-03-20T12:20:53Z","timestamp":1363782053000},"page":"32","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Mutation detection in cholestatic patients using microarray resequencing of ATP8B1 and ABCB11"],"prefix":"10.12688","volume":"2","author":[{"given":"Kirsten E","family":"McKay","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher K","family":"Bruce","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane L","family":"Hartley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A S","family":"Knisely","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Baumann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonja-Stephanie","family":"Bockisch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekkehard","family":"Sturm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian J","family":"Hendriksz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deidre A","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiona","family":"Macdonald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Gissen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2013,3,20]]},"reference":[{"key":"ref-1","doi-asserted-by":"crossref","DOI":"10.1017\/CBO9780511547409","article-title":"Liver disease in children.","author":"F Suchy","year":"2007"},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"119-126","DOI":"10.1053\/j.gastro.2006.10.034","article-title":"Novel resequencing chip customized to diagnose mutations in patients with inherited syndromes of intrahepatic cholestasis.","volume":"132","author":"C Liu","year":"2007","journal-title":"Gastroenterology."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"1656-64","DOI":"10.1002\/humu.22155","article-title":"Association among genotype, clinical phenotype and intracellular localization of trafficking proteins in ARC Syndrome.","volume":"33","author":"H Smith","year":"2012","journal-title":"Hum Mutat."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"858-865","DOI":"10.1002\/humu.21261","article-title":"Design and validation of a metabolic disorder resequencing microarray (BRUM1).","volume":"31","author":"C Bruce","year":"2010","journal-title":"Hum Mutat."},{"key":"ref-5","article-title":"Human Gene Mutation Database."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"170-8","DOI":"10.1016\/j.jhep.2010.01.034","article-title":"Differences in presentation and progression between severe FIC1 and BSEP deficiencies.","volume":"53","author":"L Pawlikowska","year":"2010","journal-title":"J Hepatol."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"553-567","DOI":"10.1002\/hep.22683","article-title":"Missense Mutations and Single Nucleotide Polymorphisms in ABCB11 Impair Bile Salt Export Pump Processing and Function or Disrupt Pre-Messenger RNA Splicing.","volume":"49","author":"J Byrne","year":"2009","journal-title":"Hepatology."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"379-384","DOI":"10.1053\/j.gastro.2004.04.065","article-title":"Benign Recurrent Intrahepatic Cholestasis Type 2 Is Caused by Mutations in ABCB11.","volume":"127","author":"S van Mil","year":"2004","journal-title":"Gastroenterology."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"27-38","DOI":"10.1002\/hep.20285","article-title":"Characterization of Mutations in ATP8B1 Associated With Hereditary Cholestasis.","volume":"40","author":"L Klomp","year":"2004","journal-title":"Hepatology."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"1203-1214","DOI":"10.1053\/j.gastro.2008.01.038","article-title":"Severe Bile Salt Export Pump Deficiency: 82 Different ABCB11 Mutations in 109 Families.","volume":"134","author":"S Strautnieks","year":"2008","journal-title":"Gastroenterology."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"1337-1341","DOI":"10.1053\/jhep.2000.20520","article-title":"A Missense Mutation in FIC1 Is Associated With Greenland Familial Cholestasis.","volume":"32","author":"L Klomp","year":"2000","journal-title":"Hepatology."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"809-15","DOI":"10.1111\/j.1478-3231.2009.02112.x","article-title":"ABCB11 gene mutations in Chinese children with progressive intrahepatic cholestasis and low gamma glutamyltransferase.","volume":"30","author":"L Liu","year":"2010","journal-title":"Liver Int."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/2-32\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/2-32\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/2-32\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,11,30]],"date-time":"2018-11-30T14:06:39Z","timestamp":1543586799000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/2-32\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3,20]]},"references-count":12,"aliases":["10.12688\/f1000research.2-32.v1"],"URL":"https:\/\/doi.org\/10.12688\/f1000research.2-32.v2","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.1255.r1619","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.1255.r1812","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.1255.r1812","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.1255.r1619","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,3,20]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/2-32\/v2#article-reports","order":0,"name":"referee-status","label":"Referee 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Medical Centre, Nijmegen, The Netherlands, 13 Sep 2013, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/2-32\/v2#referee-response-1812","order":2,"name":"referee-response-1812","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The funding for reagents was supported by an educational grant from Actelion Pharmaceuticals.","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}