HEREDITARY CHOLESTASIS: CLINICAL EXOME PANEL (Sec. & CNVs) – 140 genes

The Hereditary Cholestasis Panel is designed for the genetic diagnosis of a broad group of congenital disorders that affect the synthesis, transport, secretion, or regulation of hepatic bile acids and phospholipids. These alterations lead to reduced or absent bile flow (cholestasis), with clinical manifestations including persistent jaundice, intense pruritus, hepatomegaly, steatorrhea, fat-soluble vitamin deficiencies, failure to thrive, or progressive liver failure. In some cases, episodic cholestasis, intrahepatic cholestasis, or cholangiopathy associated with systemic malformations may occur. The panel covers genes involved in progressive familial intrahepatic cholestasis (PFIC types 1–6: ATP8B1, ABCB11, ABCB4, TJP2, NR1H4, MYO5B), Alagille syndrome (JAG1, NOTCH2), bile acid synthesis defects (AMACR, AKR1D1, HSD3B7, CYP7A1, CYP27A1, ACOX1), peroxisomal metabolism disorders (PEX1–PEX26), alpha-1-antitrypsin deficiencies (SERPINA1), canalicular defect cholestasis (ABCB11, ABCB4, ATP8B1, SLC10A1, SLCO1B1, SLCO1B3), and metabolic diseases with secondary cholestasis (CFTR, MPV17, POLG, TRMU, DGUOK, among others). Genetic testing using sequencing and CNV analysis allows for the detection of pathogenic variants or deletions/duplications responsible for cholestasis of genetic origin, facilitating differential diagnosis with acquired causes, guiding therapeutic management (ursodeoxycholic acid, ASBT inhibitors, liver transplantation), and providing prognostic information and family counseling. Key genes analyzed include: ABCB11, ABCB4, ATP8B1, JAG1, NOTCH2, SERPINA1, SLC10A1, SLCO1B1, SLCO1B3, UGT1A1, and others. A complete list of analyzed genes can be obtained by contacting Genotica.