Intrahepatic Biliary Anomalies in a Patient With Mowat‐Wilson Syndrome Uncover a Role for the Zinc Finger Homeobox Gene zfhx1b in Vertebrate Biliary Development
ABSTRACT Background: zfhz1b is the causative gene for Mowat‐Wilson syndrome, in which patients demonstrate developmental delay and Hirschsprung disease, as well as other anomalies. Materials and Methods: We identified a patient with Mowat‐Wilson syndrome who also developed cholestasis and histopatho...
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| Veröffentlicht in: | Journal of pediatric gastroenterology and nutrition 2011-03, Vol.52 (3), p.339-344 |
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| container_title | Journal of pediatric gastroenterology and nutrition |
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| creator | Cui, Shuang Erlichman, Jessi Russo, Pierre Haber, Barbara A Matthews, Randolph P |
| description | ABSTRACT
Background:
zfhz1b is the causative gene for Mowat‐Wilson syndrome, in which patients demonstrate developmental delay and Hirschsprung disease, as well as other anomalies.
Materials and Methods:
We identified a patient with Mowat‐Wilson syndrome who also developed cholestasis and histopathologic features consistent with biliary atresia, suggesting that mutations involving zfhz1b may lead to biliary developmental anomalies or injury to the biliary tract. We used the zebrafish model system to determine whether zfhx1b has a role in vertebrate biliary development.
Results:
Using zebrafish we determined that zfhx1b was expressed in the developing liver during biliary growth and remodeling, and that morpholino antisense oligonucleotide–mediated knockdown of zfhx1b led to defects in biliary development. These findings were associated with decreased expression of vhnf1, a transcription factor known to be important in biliary development in zebrafish and in mammals.
Conclusions:
Our studies underscore the importance of genetic contributions in the etiology of infantile hepatobiliary disorders, including biliary atresia. |
| doi_str_mv | 10.1097/MPG.0b013e3181ff2e5b |
| format | Article |
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Background:
zfhz1b is the causative gene for Mowat‐Wilson syndrome, in which patients demonstrate developmental delay and Hirschsprung disease, as well as other anomalies.
Materials and Methods:
We identified a patient with Mowat‐Wilson syndrome who also developed cholestasis and histopathologic features consistent with biliary atresia, suggesting that mutations involving zfhz1b may lead to biliary developmental anomalies or injury to the biliary tract. We used the zebrafish model system to determine whether zfhx1b has a role in vertebrate biliary development.
Results:
Using zebrafish we determined that zfhx1b was expressed in the developing liver during biliary growth and remodeling, and that morpholino antisense oligonucleotide–mediated knockdown of zfhx1b led to defects in biliary development. These findings were associated with decreased expression of vhnf1, a transcription factor known to be important in biliary development in zebrafish and in mammals.
Conclusions:
Our studies underscore the importance of genetic contributions in the etiology of infantile hepatobiliary disorders, including biliary atresia.</description><identifier>ISSN: 0277-2116</identifier><identifier>EISSN: 1536-4801</identifier><identifier>DOI: 10.1097/MPG.0b013e3181ff2e5b</identifier><identifier>PMID: 21336163</identifier><identifier>CODEN: JPGND6</identifier><language>eng</language><publisher>Hagerstown, MD: Copyright by ESPGHAN and NASPGHAN</publisher><subject>Animals ; biliary atresia ; Biliary Atresia - etiology ; Biliary Atresia - genetics ; Biliary Atresia - metabolism ; Biliary Tract - abnormalities ; Biliary Tract - growth & development ; Biological and medical sciences ; cholestatic liver disease ; Facies ; Feeding. Feeding behavior ; Fundamental and applied biological sciences. Psychology ; Gastroenterology. Liver. Pancreas. Abdomen ; Genes, Homeobox ; Hepatocyte Nuclear Factor 1-beta - metabolism ; Hirschsprung disease ; Hirschsprung Disease - complications ; Hirschsprung Disease - genetics ; Hirschsprung Disease - metabolism ; Homeodomain Proteins - genetics ; Homeodomain Proteins - metabolism ; Humans ; Infant ; Intellectual Disability - complications ; Intellectual Disability - genetics ; Intellectual Disability - metabolism ; Liver - metabolism ; liver development ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Malformations ; Medical sciences ; Microcephaly - complications ; Microcephaly - genetics ; Microcephaly - metabolism ; Mutation ; Oligoribonucleotides, Antisense - pharmacology ; Other diseases. Semiology ; Repressor Proteins - genetics ; Repressor Proteins - metabolism ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Vertebrates: anatomy and physiology, studies on body, several organs or systems ; Zebrafish ; zfhx1b ; Zinc Finger E-box Binding Homeobox 2 ; Zinc Fingers</subject><ispartof>Journal of pediatric gastroenterology and nutrition, 2011-03, Vol.52 (3), p.339-344</ispartof><rights>2011 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition</rights><rights>Copyright 2011 by ESPGHAN and NASPGHAN</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c536b-eadf6c47e343456e672fcbd3971f65bf3bfcc9f5c4574eb601d590aa04c879163</citedby><cites>FETCH-LOGICAL-c536b-eadf6c47e343456e672fcbd3971f65bf3bfcc9f5c4574eb601d590aa04c879163</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1097%2FMPG.0b013e3181ff2e5b$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1097%2FMPG.0b013e3181ff2e5b$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23917742$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21336163$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cui, Shuang</creatorcontrib><creatorcontrib>Erlichman, Jessi</creatorcontrib><creatorcontrib>Russo, Pierre</creatorcontrib><creatorcontrib>Haber, Barbara A</creatorcontrib><creatorcontrib>Matthews, Randolph P</creatorcontrib><title>Intrahepatic Biliary Anomalies in a Patient With Mowat‐Wilson Syndrome Uncover a Role for the Zinc Finger Homeobox Gene zfhx1b in Vertebrate Biliary Development</title><title>Journal of pediatric gastroenterology and nutrition</title><addtitle>J Pediatr Gastroenterol Nutr</addtitle><description>ABSTRACT
Background:
zfhz1b is the causative gene for Mowat‐Wilson syndrome, in which patients demonstrate developmental delay and Hirschsprung disease, as well as other anomalies.
Materials and Methods:
We identified a patient with Mowat‐Wilson syndrome who also developed cholestasis and histopathologic features consistent with biliary atresia, suggesting that mutations involving zfhz1b may lead to biliary developmental anomalies or injury to the biliary tract. We used the zebrafish model system to determine whether zfhx1b has a role in vertebrate biliary development.
Results:
Using zebrafish we determined that zfhx1b was expressed in the developing liver during biliary growth and remodeling, and that morpholino antisense oligonucleotide–mediated knockdown of zfhx1b led to defects in biliary development. These findings were associated with decreased expression of vhnf1, a transcription factor known to be important in biliary development in zebrafish and in mammals.
Conclusions:
Our studies underscore the importance of genetic contributions in the etiology of infantile hepatobiliary disorders, including biliary atresia.</description><subject>Animals</subject><subject>biliary atresia</subject><subject>Biliary Atresia - etiology</subject><subject>Biliary Atresia - genetics</subject><subject>Biliary Atresia - metabolism</subject><subject>Biliary Tract - abnormalities</subject><subject>Biliary Tract - growth & development</subject><subject>Biological and medical sciences</subject><subject>cholestatic liver disease</subject><subject>Facies</subject><subject>Feeding. Feeding behavior</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Genes, Homeobox</subject><subject>Hepatocyte Nuclear Factor 1-beta - metabolism</subject><subject>Hirschsprung disease</subject><subject>Hirschsprung Disease - complications</subject><subject>Hirschsprung Disease - genetics</subject><subject>Hirschsprung Disease - metabolism</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Humans</subject><subject>Infant</subject><subject>Intellectual Disability - complications</subject><subject>Intellectual Disability - genetics</subject><subject>Intellectual Disability - metabolism</subject><subject>Liver - metabolism</subject><subject>liver development</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Malformations</subject><subject>Medical sciences</subject><subject>Microcephaly - complications</subject><subject>Microcephaly - genetics</subject><subject>Microcephaly - metabolism</subject><subject>Mutation</subject><subject>Oligoribonucleotides, Antisense - pharmacology</subject><subject>Other diseases. Semiology</subject><subject>Repressor Proteins - genetics</subject><subject>Repressor Proteins - metabolism</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><subject>Zebrafish</subject><subject>zfhx1b</subject><subject>Zinc Finger E-box Binding Homeobox 2</subject><subject>Zinc Fingers</subject><issn>0277-2116</issn><issn>1536-4801</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkcFuEzEURUcIREvhDxDyBrFKscdjO7Ng0RaSFrUQAaUSm5HtPDMGjx1sp2lY8Ql8A5_Gl-AqoUhsYPUW79x3r32r6iHB-wS34unZbLqPFSYUKBkTY2pg6la1Sxjlo2aMye1qF9dCjGpC-E51L6VPGGPRMHy32qkJpZxwulv9OPE5yh4WMluNDq2zMq7RgQ-DdBYSsh5JNCtL8Bld2Nyjs7CS-ee37xfWpeDR27WfxzAAOvc6XEIs-JvgAJkQUe4BfbBeo4n1H8vquHBBhSs0BQ_oq-mviLp2eA8xg4oyw02C53AJLiyGYnu_umOkS_BgO_eq88mLd0fHo9PX05Ojg9ORLk9WI5Bzw3UjgDa0YRy4qI1Wc9oKYjhThiqjdWuYbphoQHFM5qzFUuJGj0VbPmOverK5u4jhyxJS7gabNDgnPYRl6saMtm3NBStksyF1DClFMN0i2qHE7gjursvpSjnd3-UU2aOtwVINML8R_W6jAI-3gExaOhOl1zb94WhLhGjqwo033Cq4DDF9dssVxK4H6XL_rwzPtlLrYP1fubuXs1f0cIIZbzn9Baq8wbk</recordid><startdate>201103</startdate><enddate>201103</enddate><creator>Cui, Shuang</creator><creator>Erlichman, Jessi</creator><creator>Russo, Pierre</creator><creator>Haber, Barbara A</creator><creator>Matthews, Randolph P</creator><general>Copyright by ESPGHAN and NASPGHAN</general><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201103</creationdate><title>Intrahepatic Biliary Anomalies in a Patient With Mowat‐Wilson Syndrome Uncover a Role for the Zinc Finger Homeobox Gene zfhx1b in Vertebrate Biliary Development</title><author>Cui, Shuang ; Erlichman, Jessi ; Russo, Pierre ; Haber, Barbara A ; Matthews, Randolph P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c536b-eadf6c47e343456e672fcbd3971f65bf3bfcc9f5c4574eb601d590aa04c879163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>biliary atresia</topic><topic>Biliary Atresia - etiology</topic><topic>Biliary Atresia - genetics</topic><topic>Biliary Atresia - metabolism</topic><topic>Biliary Tract - abnormalities</topic><topic>Biliary Tract - growth & development</topic><topic>Biological and medical sciences</topic><topic>cholestatic liver disease</topic><topic>Facies</topic><topic>Feeding. Feeding behavior</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Genes, Homeobox</topic><topic>Hepatocyte Nuclear Factor 1-beta - metabolism</topic><topic>Hirschsprung disease</topic><topic>Hirschsprung Disease - complications</topic><topic>Hirschsprung Disease - genetics</topic><topic>Hirschsprung Disease - metabolism</topic><topic>Homeodomain Proteins - genetics</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Humans</topic><topic>Infant</topic><topic>Intellectual Disability - complications</topic><topic>Intellectual Disability - genetics</topic><topic>Intellectual Disability - metabolism</topic><topic>Liver - metabolism</topic><topic>liver development</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Malformations</topic><topic>Medical sciences</topic><topic>Microcephaly - complications</topic><topic>Microcephaly - genetics</topic><topic>Microcephaly - metabolism</topic><topic>Mutation</topic><topic>Oligoribonucleotides, Antisense - pharmacology</topic><topic>Other diseases. Semiology</topic><topic>Repressor Proteins - genetics</topic><topic>Repressor Proteins - metabolism</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>Vertebrates: anatomy and physiology, studies on body, several organs or systems</topic><topic>Zebrafish</topic><topic>zfhx1b</topic><topic>Zinc Finger E-box Binding Homeobox 2</topic><topic>Zinc Fingers</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cui, Shuang</creatorcontrib><creatorcontrib>Erlichman, Jessi</creatorcontrib><creatorcontrib>Russo, Pierre</creatorcontrib><creatorcontrib>Haber, Barbara A</creatorcontrib><creatorcontrib>Matthews, Randolph P</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of pediatric gastroenterology and nutrition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cui, Shuang</au><au>Erlichman, Jessi</au><au>Russo, Pierre</au><au>Haber, Barbara A</au><au>Matthews, Randolph P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intrahepatic Biliary Anomalies in a Patient With Mowat‐Wilson Syndrome Uncover a Role for the Zinc Finger Homeobox Gene zfhx1b in Vertebrate Biliary Development</atitle><jtitle>Journal of pediatric gastroenterology and nutrition</jtitle><addtitle>J Pediatr Gastroenterol Nutr</addtitle><date>2011-03</date><risdate>2011</risdate><volume>52</volume><issue>3</issue><spage>339</spage><epage>344</epage><pages>339-344</pages><issn>0277-2116</issn><eissn>1536-4801</eissn><coden>JPGND6</coden><abstract>ABSTRACT
Background:
zfhz1b is the causative gene for Mowat‐Wilson syndrome, in which patients demonstrate developmental delay and Hirschsprung disease, as well as other anomalies.
Materials and Methods:
We identified a patient with Mowat‐Wilson syndrome who also developed cholestasis and histopathologic features consistent with biliary atresia, suggesting that mutations involving zfhz1b may lead to biliary developmental anomalies or injury to the biliary tract. We used the zebrafish model system to determine whether zfhx1b has a role in vertebrate biliary development.
Results:
Using zebrafish we determined that zfhx1b was expressed in the developing liver during biliary growth and remodeling, and that morpholino antisense oligonucleotide–mediated knockdown of zfhx1b led to defects in biliary development. These findings were associated with decreased expression of vhnf1, a transcription factor known to be important in biliary development in zebrafish and in mammals.
Conclusions:
Our studies underscore the importance of genetic contributions in the etiology of infantile hepatobiliary disorders, including biliary atresia.</abstract><cop>Hagerstown, MD</cop><pub>Copyright by ESPGHAN and NASPGHAN</pub><pmid>21336163</pmid><doi>10.1097/MPG.0b013e3181ff2e5b</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0277-2116 |
| ispartof | Journal of pediatric gastroenterology and nutrition, 2011-03, Vol.52 (3), p.339-344 |
| issn | 0277-2116 1536-4801 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_853992675 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Journals@Ovid Complete |
| subjects | Animals biliary atresia Biliary Atresia - etiology Biliary Atresia - genetics Biliary Atresia - metabolism Biliary Tract - abnormalities Biliary Tract - growth & development Biological and medical sciences cholestatic liver disease Facies Feeding. Feeding behavior Fundamental and applied biological sciences. Psychology Gastroenterology. Liver. Pancreas. Abdomen Genes, Homeobox Hepatocyte Nuclear Factor 1-beta - metabolism Hirschsprung disease Hirschsprung Disease - complications Hirschsprung Disease - genetics Hirschsprung Disease - metabolism Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Humans Infant Intellectual Disability - complications Intellectual Disability - genetics Intellectual Disability - metabolism Liver - metabolism liver development Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Malformations Medical sciences Microcephaly - complications Microcephaly - genetics Microcephaly - metabolism Mutation Oligoribonucleotides, Antisense - pharmacology Other diseases. Semiology Repressor Proteins - genetics Repressor Proteins - metabolism Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Vertebrates: anatomy and physiology, studies on body, several organs or systems Zebrafish zfhx1b Zinc Finger E-box Binding Homeobox 2 Zinc Fingers |
| title | Intrahepatic Biliary Anomalies in a Patient With Mowat‐Wilson Syndrome Uncover a Role for the Zinc Finger Homeobox Gene zfhx1b in Vertebrate Biliary Development |
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