Dataset Information
Whole exome sequencing identifies recessive PKHD1 mutations in a Chinese twin family with Caroli disease.
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ABSTRACT: Background
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.Methods
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.Results
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.Conclusions
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.
SUBMITTER: Hao X
PROVIDER: S-EPMC3977808 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
Publications
Whole exome sequencing identifies recessive PKHD1 mutations in a Chinese twin family with Caroli disease.
PloS one 20140407 4
<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 ...[more]