Whole exome sequencing identifies recessive PKHD1 mutations in a Chinese twin family with Caroli disease.
<h4>Background</h4>Mutations in PKHD1 cause autosomal recessive Caroli disease, which is a rare congenital disorder involving cystic dilatation of the intrahepatic bile ducts. However, the mutational spectrum of PKHD1 and the phenotype-genotype correlations have not yet been fully establ...
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0092661&type=printable |
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| author | Xiwei Hao Shiguo Liu Qian Dong Hong Zhang Jing Zhao Lin Su |
| author_facet | Xiwei Hao Shiguo Liu Qian Dong Hong Zhang Jing Zhao Lin Su |
| author_sort | Xiwei Hao |
| collection | DOAJ |
| description | <h4>Background</h4>Mutations in PKHD1 cause autosomal recessive Caroli disease, which is a rare congenital disorder involving cystic dilatation of the intrahepatic bile ducts. However, the mutational spectrum of PKHD1 and the phenotype-genotype correlations have not yet been fully established.<h4>Methods</h4>Whole exome sequencing (WES) was performed on one twin sample with Caroli disease from a Chinese family from Shandong province. Routine Sanger sequencing was used to validate the WES and to carry out segregation studies. We also described the PKHD1 mutation associated with the genotype-phenotype of this twin.<h4>Results</h4>A combination of WES and Sanger sequencing revealed the genetic defect to be a novel compound heterozygous genotype in PKHD1, including the missense mutation c.2507 T>C, predicted to cause a valine to alanine substitution at codon 836 (c.2507T>C, p.Val836Ala), and the nonsense mutation c.2341C>T, which is predicted to result in an arginine to stop codon at codon 781 (c.2341C>T, p.Arg781*). This compound heterozygous genotype co-segregates with the Caroli disease-affected pedigree members, but is absent in 200 normal chromosomes.<h4>Conclusions</h4>Our findings indicate exome sequencing can be useful in the diagnosis of Caroli disease patients and associate a compound heterozygous genotype in PKHD1 with Caroli disease, which further increases our understanding of the mutation spectrum of PKHD1 in association with Caroli disease. |
| format | Article |
| id | doaj-art-280d5cf06c2a424784442a45b5201e7a |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj-art-280d5cf06c2a424784442a45b5201e7a2025-08-20T02:14:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9266110.1371/journal.pone.0092661Whole exome sequencing identifies recessive PKHD1 mutations in a Chinese twin family with Caroli disease.Xiwei HaoShiguo LiuQian DongHong ZhangJing ZhaoLin Su<h4>Background</h4>Mutations in PKHD1 cause autosomal recessive Caroli disease, which is a rare congenital disorder involving cystic dilatation of the intrahepatic bile ducts. However, the mutational spectrum of PKHD1 and the phenotype-genotype correlations have not yet been fully established.<h4>Methods</h4>Whole exome sequencing (WES) was performed on one twin sample with Caroli disease from a Chinese family from Shandong province. Routine Sanger sequencing was used to validate the WES and to carry out segregation studies. We also described the PKHD1 mutation associated with the genotype-phenotype of this twin.<h4>Results</h4>A combination of WES and Sanger sequencing revealed the genetic defect to be a novel compound heterozygous genotype in PKHD1, including the missense mutation c.2507 T>C, predicted to cause a valine to alanine substitution at codon 836 (c.2507T>C, p.Val836Ala), and the nonsense mutation c.2341C>T, which is predicted to result in an arginine to stop codon at codon 781 (c.2341C>T, p.Arg781*). This compound heterozygous genotype co-segregates with the Caroli disease-affected pedigree members, but is absent in 200 normal chromosomes.<h4>Conclusions</h4>Our findings indicate exome sequencing can be useful in the diagnosis of Caroli disease patients and associate a compound heterozygous genotype in PKHD1 with Caroli disease, which further increases our understanding of the mutation spectrum of PKHD1 in association with Caroli disease.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0092661&type=printable |
| spellingShingle | Xiwei Hao Shiguo Liu Qian Dong Hong Zhang Jing Zhao Lin Su Whole exome sequencing identifies recessive PKHD1 mutations in a Chinese twin family with Caroli disease. PLoS ONE |
| title | Whole exome sequencing identifies recessive PKHD1 mutations in a Chinese twin family with Caroli disease. |
| title_full | Whole exome sequencing identifies recessive PKHD1 mutations in a Chinese twin family with Caroli disease. |
| title_fullStr | Whole exome sequencing identifies recessive PKHD1 mutations in a Chinese twin family with Caroli disease. |
| title_full_unstemmed | Whole exome sequencing identifies recessive PKHD1 mutations in a Chinese twin family with Caroli disease. |
| title_short | Whole exome sequencing identifies recessive PKHD1 mutations in a Chinese twin family with Caroli disease. |
| title_sort | whole exome sequencing identifies recessive pkhd1 mutations in a chinese twin family with caroli disease |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0092661&type=printable |
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