<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>1665-2681</journal-id>
<journal-title><![CDATA[Annals of Hepatology]]></journal-title>
<abbrev-journal-title><![CDATA[Ann. Hepatol.]]></abbrev-journal-title>
<issn>1665-2681</issn>
<publisher>
<publisher-name><![CDATA[Asociación Mexicana de Hepatología A.C.]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S1665-26812017000300465</article-id>
<article-id pub-id-type="doi">10.5604/16652681.1235494</article-id>
<title-group>
<article-title xml:lang="en"><![CDATA[A Rare BSEP Mutation Associated with a Mild Form of Progressive Familial Intrahepatic Cholestasis Type 2]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Waisbourd-Zinman]]></surname>
<given-names><![CDATA[Orith]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aaf"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Surrey]]></surname>
<given-names><![CDATA[Lea F.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Schwartz]]></surname>
<given-names><![CDATA[Anna E.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Russo]]></surname>
<given-names><![CDATA[Pierre A.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aaf"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Wen]]></surname>
<given-names><![CDATA[Jessica]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aaf"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Children&#8217;s Hospital of Philadelphia Division of Gastroenterology, Hepatology and Nutrition ]]></institution>
<addr-line><![CDATA[Philadelphia PA]]></addr-line>
<country>USA</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Tel-Aviv University Sackler Faculty of Medicine Schneider Children&#8217;s Medical Center of Israel]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
<country>Israel</country>
</aff>
<aff id="Af3">
<institution><![CDATA[,Children&#8217;s Hospital of Philadelphia Department of Pathology and Laboratory Medicine ]]></institution>
<addr-line><![CDATA[Philadelphia PA]]></addr-line>
<country>USA</country>
</aff>
<aff id="Af4">
<institution><![CDATA[,University of Pennsylvania Perelman School of Medicine ]]></institution>
<addr-line><![CDATA[ Philadelphia]]></addr-line>
<country>USA</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>06</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>06</month>
<year>2017</year>
</pub-date>
<volume>16</volume>
<numero>3</numero>
<fpage>465</fpage>
<lpage>468</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_arttext&amp;pid=S1665-26812017000300465&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_abstract&amp;pid=S1665-26812017000300465&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_pdf&amp;pid=S1665-26812017000300465&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="en"><p><![CDATA[ABSTRACT Progressive Familial Intrahepatic Cholestasis type 2 (PFIC2) is a rare cholestatic disorder diagnosed in infancy or childhood that can lead to severe hepatic fibrosis and liver failure. Mutations in the ABCB11 gene result in a deficiency of the bile salt export protein (BSEP) and accumulation of bile inside the hepatocytes. Hepatocellular carcinoma is another condition associated with severe forms of deletion mutations in the ABCB11 gene. Treatment options including ursodeoxycholic acid biliary diversion have mixed outcomes and some patients require liver transplantation. Here, we describe two siblings with an extremely mild form of PFIC2 inherited from heterozygous parents. The elder sibling had acute liver failure at the age of six months and both siblings had pruritus, cholestasis, coagulopathy and fat-soluble-vitamin deficiencies in infancy but have been asymptomatic past infancy. Genetic testing of the siblings revealed that each were compound heterozygotes for two missense mutations of the ABCB11 gene: p.C68Y and p.R832H. Medical treatment typical for PFIC2 has not been necessary for either patient. This is the first report of these variants following a mild course in two affected patients.]]></p></abstract>
<kwd-group>
<kwd lng="en"><![CDATA[Cholestasis]]></kwd>
<kwd lng="en"><![CDATA[PFIC2]]></kwd>
<kwd lng="en"><![CDATA[Progressive Familial Intrahepatic Cholestasis]]></kwd>
<kwd lng="en"><![CDATA[ABCB11]]></kwd>
<kwd lng="en"><![CDATA[BSEP]]></kwd>
</kwd-group>
</article-meta>
</front><back>
<ref-list>
<ref id="B1">
<nlm-citation citation-type="journal">
<article-title xml:lang=""><![CDATA[Hepatocellular Carcinoma in a Boy with Progressive familial Intrahepatic Cholestasis Type II Challenging Identification: Case report]]></article-title>
<person-group person-group-type="author">
<name>
<surname><![CDATA[Alsalloom]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
</person-group>
<source><![CDATA[Int J Health Sci (Qassim)]]></source>
<year>2013</year>
<volume>7</volume>
<page-range>252-5</page-range></nlm-citation>
</ref>
<ref id="B2">
<nlm-citation citation-type="journal">
<article-title xml:lang=""><![CDATA[The spectrum of liver diseases related to ABCB4 gene mutations pathophysiology and clinical aspects]]></article-title>
<person-group person-group-type="author">
<name>
<surname><![CDATA[Davit-Spraul]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Gonzales]]></surname>
<given-names><![CDATA[E]]></given-names>
</name>
<name>
<surname><![CDATA[Baussan]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Jacquemin]]></surname>
<given-names><![CDATA[E]]></given-names>
</name>
</person-group>
<source><![CDATA[Semin Liver Dis]]></source>
<year>2010</year>
<volume>30</volume>
<page-range>134-46</page-range></nlm-citation>
</ref>
<ref id="B3">
<nlm-citation citation-type="journal">
<article-title xml:lang=""><![CDATA[Preoperative observations and short-term outcome after partial external biliary diversion in 13 patients with progressive familial intrahepatic cholestasis]]></article-title>
<person-group person-group-type="author">
<name>
<surname><![CDATA[Arnell]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
<name>
<surname><![CDATA[Bergdahl]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Papadogiannakis]]></surname>
<given-names><![CDATA[N]]></given-names>
</name>
<name>
<surname><![CDATA[Nemeth]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Fischler]]></surname>
<given-names><![CDATA[B]]></given-names>
</name>
</person-group>
<source><![CDATA[J Pediatr Surg]]></source>
<year>2008</year>
<volume>43</volume>
<page-range>1312-20</page-range></nlm-citation>
</ref>
<ref id="B4">
<nlm-citation citation-type="journal">
<article-title xml:lang=""><![CDATA[Ursodeoxycholic acid therapy in pediatric patients with progressive familial intrahepatic cholestasis]]></article-title>
<person-group person-group-type="author">
<name>
<surname><![CDATA[Jacquemin]]></surname>
<given-names><![CDATA[E]]></given-names>
</name>
<name>
<surname><![CDATA[Hermans]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Myara]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Habes]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Debray]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Hadchouel]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Sokal]]></surname>
<given-names><![CDATA[EM]]></given-names>
</name>
</person-group>
<source><![CDATA[Hepatology]]></source>
<year>1997</year>
<volume>25</volume>
<page-range>519-23</page-range></nlm-citation>
</ref>
<ref id="B5">
<nlm-citation citation-type="journal">
<article-title xml:lang=""><![CDATA[Progressive familial intrahepatic cholestasis]]></article-title>
<person-group person-group-type="author">
<name>
<surname><![CDATA[Srivastava]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
</person-group>
<source><![CDATA[J Clin Exp Hepatol]]></source>
<year>2014</year>
<volume>4</volume>
<page-range>25-36</page-range></nlm-citation>
</ref>
<ref id="B6">
<nlm-citation citation-type="journal">
<article-title xml:lang=""><![CDATA[Molecular pathogenesis of cholestasis]]></article-title>
<person-group person-group-type="author">
<name>
<surname><![CDATA[Trauner]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Meier]]></surname>
<given-names><![CDATA[PJ]]></given-names>
</name>
<name>
<surname><![CDATA[Boyer]]></surname>
<given-names><![CDATA[JL]]></given-names>
</name>
</person-group>
<source><![CDATA[N Engl J Med]]></source>
<year>1998</year>
<volume>339</volume>
<page-range>1217-27</page-range></nlm-citation>
</ref>
<ref id="B7">
<nlm-citation citation-type="journal">
<article-title xml:lang=""><![CDATA[Morphologic findings in progressive familial intrahepatic cholestasis 2 (PFIC2) correlation with genetic and immunohistochemical studies]]></article-title>
<person-group person-group-type="author">
<name>
<surname><![CDATA[Evason]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
<name>
<surname><![CDATA[Bove]]></surname>
<given-names><![CDATA[KE]]></given-names>
</name>
<name>
<surname><![CDATA[Finegold]]></surname>
<given-names><![CDATA[MJ]]></given-names>
</name>
<name>
<surname><![CDATA[Knisely]]></surname>
<given-names><![CDATA[AS]]></given-names>
</name>
<name>
<surname><![CDATA[Rhee]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Rosenthal]]></surname>
<given-names><![CDATA[P]]></given-names>
</name>
<name>
<surname><![CDATA[Miethke]]></surname>
<given-names><![CDATA[AG]]></given-names>
</name>
</person-group>
<source><![CDATA[Am J Surg Pathol]]></source>
<year>2011</year>
<volume>35</volume>
<page-range>687-96</page-range></nlm-citation>
</ref>
<ref id="B8">
<nlm-citation citation-type="journal">
<article-title xml:lang=""><![CDATA[Differences in presentation and progression between severe FIC1 and BSEP deficiencies]]></article-title>
<person-group person-group-type="author">
<name>
<surname><![CDATA[Pawlikowska]]></surname>
<given-names><![CDATA[L]]></given-names>
</name>
<name>
<surname><![CDATA[Strautnieks]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Jankowska]]></surname>
<given-names><![CDATA[I]]></given-names>
</name>
<name>
<surname><![CDATA[Czubkowski]]></surname>
<given-names><![CDATA[P]]></given-names>
</name>
<name>
<surname><![CDATA[Emerick]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
<name>
<surname><![CDATA[Antoniou]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Wanty]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
</person-group>
<source><![CDATA[J Hepatol]]></source>
<year>2010</year>
<volume>53</volume>
<page-range>170-8</page-range></nlm-citation>
</ref>
<ref id="B9">
<nlm-citation citation-type="journal">
<article-title xml:lang=""><![CDATA[ATP8B1 and ABCB11 analysis in 62 children with normal gamma-glutamyl transferase progressive familial intrahepatic cholestasis (PFIC) phenotypic differences between PFIC1 and PFIC2 and natural history]]></article-title>
<person-group person-group-type="author">
<name>
<surname><![CDATA[Davit-Spraul]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Fabre]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Branchereau]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Baussan]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Gonzáles]]></surname>
<given-names><![CDATA[E]]></given-names>
</name>
<name>
<surname><![CDATA[Stieger]]></surname>
<given-names><![CDATA[B]]></given-names>
</name>
<name>
<surname><![CDATA[Bernard]]></surname>
<given-names><![CDATA[O]]></given-names>
</name>
</person-group>
<source><![CDATA[Hepatology]]></source>
<year>2010</year>
<volume>51</volume>
<page-range>1645-55</page-range></nlm-citation>
</ref>
<ref id="B10">
<nlm-citation citation-type="journal">
<article-title xml:lang=""><![CDATA[Familial cholestasis progressive familial intrahepatic cholestasis, benign recurrent intrahepatic cholestasis and intrahepatic cholestasis of pregnancy]]></article-title>
<person-group person-group-type="author">
<name>
<surname><![CDATA[van der Woerd]]></surname>
<given-names><![CDATA[WL]]></given-names>
</name>
<name>
<surname><![CDATA[van Mil]]></surname>
<given-names><![CDATA[SW]]></given-names>
</name>
<name>
<surname><![CDATA[Stapelbroek]]></surname>
<given-names><![CDATA[JM]]></given-names>
</name>
<name>
<surname><![CDATA[Klomp]]></surname>
<given-names><![CDATA[LW]]></given-names>
</name>
<name>
<surname><![CDATA[van de Graaf]]></surname>
<given-names><![CDATA[SF]]></given-names>
</name>
<name>
<surname><![CDATA[Houwen]]></surname>
<given-names><![CDATA[RH]]></given-names>
</name>
</person-group>
<source><![CDATA[Best Pract Res Clin Gastroenterol]]></source>
<year>2010</year>
<volume>24</volume>
<page-range>541-53</page-range></nlm-citation>
</ref>
<ref id="B11">
<nlm-citation citation-type="">
<source><![CDATA[]]></source>
<year></year>
</nlm-citation>
</ref>
<ref id="B12">
<nlm-citation citation-type="journal">
<article-title xml:lang=""><![CDATA[Standards and guidelines for the interpretation of sequence variants a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology]]></article-title>
<person-group person-group-type="author">
<name>
<surname><![CDATA[Richards]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Aziz]]></surname>
<given-names><![CDATA[N]]></given-names>
</name>
<name>
<surname><![CDATA[Bale]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Bick]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Das]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Gastier-Foster]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Grody]]></surname>
<given-names><![CDATA[VWV]]></given-names>
</name>
</person-group>
<source><![CDATA[Genet Med]]></source>
<year>2015</year>
<volume>17</volume>
<page-range>405-24</page-range></nlm-citation>
</ref>
<ref id="B13">
<nlm-citation citation-type="journal">
<article-title xml:lang=""><![CDATA[Clinical and histologic features of azithromycin-induced liver injury]]></article-title>
<person-group person-group-type="author">
<name>
<surname><![CDATA[Martinez]]></surname>
<given-names><![CDATA[MA]]></given-names>
</name>
<name>
<surname><![CDATA[Vuppalanchi]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Fontana]]></surname>
<given-names><![CDATA[RJ]]></given-names>
</name>
<name>
<surname><![CDATA[Stolz]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Kleiner]]></surname>
<given-names><![CDATA[DE]]></given-names>
</name>
<name>
<surname><![CDATA[Hayashi]]></surname>
<given-names><![CDATA[PH]]></given-names>
</name>
<name>
<surname><![CDATA[Gu]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
</person-group>
<source><![CDATA[Clin Gastroenterol Hepatol]]></source>
<year>2015</year>
<volume>13</volume>
<page-range>369-76</page-range></nlm-citation>
</ref>
<ref id="B14">
<nlm-citation citation-type="journal">
<article-title xml:lang=""><![CDATA[Benign recurrent intrahepatic cholestasis studies of bilirubin kinetics, bile acids, and cholangiography]]></article-title>
<person-group person-group-type="author">
<name>
<surname><![CDATA[Summerfield]]></surname>
<given-names><![CDATA[JA]]></given-names>
</name>
<name>
<surname><![CDATA[Scott]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Berman]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Ghent]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Bloomer]]></surname>
<given-names><![CDATA[JR]]></given-names>
</name>
<name>
<surname><![CDATA[Berk]]></surname>
<given-names><![CDATA[PD]]></given-names>
</name>
<name>
<surname><![CDATA[Sherlock]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
</person-group>
<source><![CDATA[Gut]]></source>
<year>1980</year>
<volume>21</volume>
<page-range>154-60</page-range></nlm-citation>
</ref>
</ref-list>
</back>
</article>
