Progressive Familial Intrahepatic Cholestasis Panel
Progressive Familial Intrahepatic Cholestasis (PFIC) is an inherited disorder that causes liver damage in the form of cirrhosis and related symptoms due to the accumulation of bile in the liver.
Overview
- Progressive Familial Intrahepatic Cholestasis (PFIC) is an inherited disorder that causes liver damage in the form of cirrhosis and related symptoms due to the accumulation of bile in the liver. There are three types of PFIC that are caused by changes in different genes but have similar symptoms and presentation. Individuals with PFIC1 are more severely affected and have additional health concerns on top of liver disease. Individuals with PFIC2 and PFIC3 show symptoms that are primarily associated with liver disease only and vary in age of onset and severity. All three types of PFIC are inherited in an autosomal recessive manner.
- The Igenomix Progressive Familial Intrahepatic Cholestasis Precision Panel can be used to make a directed and accurate differential diagnosis of liver disease, ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved.
Indication
The Igenomix Progressive Familial Intrahepatic Cholestasis Precision Panel is indicated for those patients with a clinical suspicion or diagnosis of hemochromatosis presenting with the following manifestations:
- Itching (pruritus)
- Yellow skin (jaundice)
- Poor growth and weight gains
- Fatigue
- Enlargement of the liver and spleen (hepatomegaly, splenomegaly)
Clinical Utility
The clinical utility of this panel is:
- The genetic and molecular confirmation for an accurate clinical diagnosis of a symptomatic patient.
- Early initiation of treatment with a multidisciplinary team for early pharmacologic treatment, surgical care, and dietary modifications.
- Risk assessment of asymptomatic family members according to the mode of inheritance.
Genes & Diseases
| GENE | OMIM DISEASES | INHERITANCE* | % GENE COVERAGE (20X) | HGMD** |
| ABCB11 | Benign Recurrent Intrahepatic Cholestasis, Progressive Familial Intrahepatic Cholestasis | AR | 99.92% | 333 of 334 |
| ABCB4 | Intrahepatic Cholestasis Of Pregnancy, Familial Intrahepatic Cholestasis, Gallbladder Disease | AD,AR | 100% | 255 of 256 |
| ATP8B1 | Benign Recurrent Intrahepatic Cholestasis, Intrahepatic Cholestasis Of Pregnancy, Progressive Familial Intrahepatic Cholestasis | AD,AR | 99.98% | 140 of 140 |
| MYO5B | Diarrhea With Microvillous Atrophy, Microvillus Inclusion Disease | AR | 100% | 86 of 86 |
| NR1H4 | Progressive Familial Intrahepatic Cholestasis | AR | 100% | 4 of 4 |
| TJP2 | Progressive Familial Intrahepatic Cholestasis, Familial Hypercholanemia | AR | 99.85% | 43 of 43 |
*Inheritance: AD: Autosomal Dominant; AR: Autosomal Recessive; X: X linked; XLR: X linked Recessive; Mi: Mitochondrial; Mu: Multifactorial.
**Number of clinically relevant mutations according to HGMD
References
Bull, L. N., & Thompson, R. J. (2018). Progressive Familial Intrahepatic Cholestasis. Clinics in liver disease, 22(4), 657–669. https://doi.org/10.1016/j.cld.2018.06.003
Baker, A., Kerkar, N., Todorova, L., Kamath, B. M., & Houwen, R. (2019). Systematic review of progressive familial intrahepatic cholestasis. Clinics and research in hepatology and gastroenterology, 43(1), 20–36. https://doi.org/10.1016/j.clinre.2018.07.010
Srivastava A. (2014). Progressive familial intrahepatic cholestasis. Journal of clinical and experimental hepatology, 4(1), 25–36. https://doi.org/10.1016/j.jceh.2013.10.005
Siddiqi, I., & Tadi, P. (2020). Progressive Familial Intrahepatic Cholestasis. In StatPearls. StatPearls Publishing.
