Paternal isodisomy of chromosome 2 in a child with bile salt export pump deficiency

We describe a child with progressive familial intrahepatic cholestasis (PFIC) of type 2 inherited as uniparental isodisomy of chromosome 2. Bile salt export pump (BSEP) deficiency is a severe, genetically determined subtype PFIC caused by mutations in ABCB11, the gene encoding a bile salt transporter protein. Clinical and pathological diagnosis in PFIC2 is corroborated by an ample array of ABCB11 mutations, inherited in an autosomal recessive fashion. We report clinical, pathological, and molecular studies in a child with PFIC2. A 5.5-year-old boy harbored a described pathogenic mutation (p.R832C) in ABCB11. The mutation was found to be homozygous in the patient and heterozygous in DNA from paternal, but not maternal blood. Having ruled out maternal gene deletion and somatic mosaicism, we showed that the child had inherited an isodisomic paternal chromosome 2, including the 2q31.1 region where ABCB11 is located. The present report is the first description of uniparental isodisomy in a hepatic heritable disorder. Recognizing isodisomic transmission may have a significant impact on genetic counseling helping to define the risk of recurrence in subsequent pregnancies.