Journal of Genetic Syndromes & Gene Therapy
Open Access

Abstract

A New Homozygous ABCB4 Mutation Identified in Two Chinese Siblings Based on Exome Sequencing

Hui Lin, Rong Fu, Xiumin Zhang, Bihui Yao, Jing Ye, Jianguo Shi, Wen Sui and Zengshan Li

Background: Many pediatric cholestatic liver diseases show unspecific symptoms, laboratory tests and histological features. A complete genetic background check is necessary to identify the genetic determinants as well as the diagnosis and differential diagnosis. Method: The whole genome exome sequencing was performed in two Chinese sister siblings with unspecific cholestasis and the data was analyzed. Results: A homozygous mutation, c.2176C-T transition (p.P726L) in exon 17 of ABCB4, was identified. Further study indicated that there are mutant alleles in the genome of their non consanguineous parents. The final diagnosis is progressive familial intrahepatic cholestasis (PFIC), type 3. Conclusion: As a rare hereditary cholestatic liver disease, PFIC shares many similar features with other hereditary or acquired liver disease and requires a wide range of differential diagnosis. Exome sequencing is a useful tool for mapping this kind of monogenic disease mutation and plays a very important role in genetic counseling and prenatal diagnosis.Background: Many pediatric cholestatic liver diseases show unspecific symptoms, laboratory tests and histological features. A complete genetic background check is necessary to identify the genetic determinants as well as the diagnosis and differential diagnosis. Method: The whole genome exome sequencing was performed in two Chinese sister siblings with unspecific cholestasis and the data was analyzed. Results: A homozygous mutation, c.2176C-T transition (p.P726L) in exon 17 of ABCB4, was identified. Further study indicated that there are mutant alleles in the genome of their non consanguineous parents. The final diagnosis is progressive familial intrahepatic cholestasis (PFIC), type 3. Conclusion: As a rare hereditary cholestatic liver disease, PFIC shares many similar features with other hereditary or acquired liver disease and requires a wide range of differential diagnosis. Exome sequencing is a useful tool for mapping this kind of monogenic disease mutation and plays a very important role in genetic counseling and prenatal diagnosis.