||This panel includes 3 types of PFIC and Alagille syndrome. Progressive familial intrahepatic cholestasis (PFIC) refers to a heterogeneous group of autosomal recessive familial cholestasis conditions caused by defects in biliary epithelial transporters. Three genes are responsible for three types of PFIC: ATP8B1 (PFIC1), ABCB11 (PFIC2) and ABCB4 (PFIC3). Clinical features of PFIC include: jaundice, early onset cholestasis with symptoms appearing as early as 3 months of age, typically severe and persistent pruritus, and failure to thrive. In the absence of surgical intervention, hepatic failure usually occurs within the first two decades of life.
Alagille syndrome is an autosomal dominant disorder caused by mutations in JAG1 gene. Alagille syndrome (AGS) is a complex multisystem disorder involving liver, heart, eyes, face, and skeleton. The liver involvement ranges from jaundice, mild cholestasis, and pruritus to progressive liver failure.
PFIC1-3 and Alagille syndrome are rare but disabling genetic disorders, with high morbidity and mortality rates, often requiring liver transplantation before the age of 10. The cholestasis panel (MitoMe-NGS) consisting of four genes, ABCB11, ATP8B1, ABCB4, and JAG1, offers a convenient one-step test for the molecular diagnosis of patients whose symptoms include cholestasis.
Four nuclear encoded genes involved in cholestasis and liver dysfunction are analyzed by the newly developed and clinically validated approach of Massively Parallel Sequencing (MPS) using Next Generation Sequence (NGS) technology. The ABCB11 (#3310), ATP8B1 (#3305), ABCB4 (#3315), JAG1 (#3755) genes are analyzed by this panel. Sanger sequencing of these genes is also available using the associated individual test codes.
All coding exons of these 4 nuclear genes and at least 20 base pairs of flanking intronic sequences are analyzed. All exonic variants and intronic variants within 20 bp of the exon/intron boundary will be reported. Sequence analysis will not detect genomic structural rearrangements (e.g. heterozygous deletions, duplications, and inversions), large heterozygous insertion mutations (e.g. ALU mediated insertion), and mutations within the promoter or deep intronic regions. Mutations and novel variants detected by NGS are confirmed by Sanger sequencing.
Mitomet deletion/duplication analysis (#2003) for the genes covered by this panel is also available.