Liver Diseases

Analysis of all known genes associated with liver diseases

The liver is the central organ for metabolism in the body and has many functions reaching from protein production and depletion to blood clotting as well as the metabolism of cholesterol, glucose and iron.

The reasons for liver diseases are often virus infections, alcohol, liver cancer, or obesity. But there could also be genetic causes. Frequent inherited liver disorders are hereditary hemochromatosis, α1-antitrypsin deficiency, or Wilson disease. Besides the transport and metabolic disturbances underlying these disorders, a malformation of the biliary tracts and other biliary tract diseases or structural impairments during organ morphogenesis can also lead to disturbance of liver function. Thus, therapy for liver diseases, which often responds well to treatment, is highly specific according to the underlying cause. Therefore, diagnosing the exact cause of the respective disease is indispensable.

The Diagnostic Panel for Liver Diseases is based on our proprietary, high-quality ExomeXtra® enrichment, covering all protein-coding regions as well as intronic and intergenic variants described as disease-relevant in the databases HGMD and ClinVar. In addition, the ExomeXtra® enrichment enables a genome-wide CNV calling with similar performance to array CGH. It thus provides the ideal basis for genetic diagnostics.

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What We Offer with the Panel for Liver Diseases

Updates

The gene selection is regularly adapted to the current scientific knowledge

Flexibility

With ExomeXtra®, gene sets addressing different diseases can be combined

Comprehensive Medical Report

Including the ACMG criteria used to classify the variants

Highest Quality

All steps are carried out in-house

Our Promise to You

Fast Turnaround Time

2–4 weeks after sample receipt

Safety

Highest confidentiality and quality standards

Reliability

Reliable support throughout all steps

Comprehensibility

Clearly prepared medical report

Your Benefits

It is possible to request single or multiple predefined gene sets. In addition to the complete analysis of the genes of the requested gene set, we extend the analysis by additional genes for differential diagnosis. We report variants of unknown significance (ACMG class 3) and pathogenic and probably pathogenic variants (ACMG classes 4 and 5) for the primarily ordered gene set. For the genes included due to differential diagnosis, we restrict the reporting to pathogenic and probably pathogenic variants (ACMG classes 4 and 5), which could be related to the indication of the person seeking advice.

The Diagnostic Panel for Liver Diseases is based on CeGaT’s ExomeXtra® enrichment. This allows, without additional sequencing, phenotypically eligible gene sets of other CeGaT panels or single genes to be additionally ordered. If you would like to assemble an individual panel, please feel free to contact us. We will be happy to support you.

In addition to the primary diagnostic assignment, the assessment of ACMG genes and pharmacogenetic profiling may also be ordered.

Method

The enrichment of the coding regions and the adjacent intronic regions is performed using an in-solution hybridization technology. The selection of the targeted regions and the design of the enrichment baits is performed in-house. High-throughput sequencing is performed on our Illumina platforms. Bioinformatic processing of the data is achieved using an in-house computer cluster.

Following data processing, our team of scientists and specialists in human genetics analyze the data and issue a medical report.

Sample Report

Information: The example report on epilepsy and brain development disorders illustrates how a report is structured.

General Information

Material

1-2 ml EDTA blood (recommended sample type) or
1-2 µg genomic DNA
Order Form with declaration of consent

Here you can find more information on how to ship your sample safely.

Costs

The prices for our human genetic diagnostics depend on the size of the selected diagnostic panel and the selected gene sets. All prices include sequencing, bioinformatic analysis, and issuing of a medical report by our team of experts in human genetic diagnostics.

Diagnostic Process

You can find the entire diagnostic process here

Counseling & Test Selection

Sampling & Shipment

Sample Analysis

Medical Report & Counseling

Gene Sets – Liver Diseases

Progressive Familial Intrahepatic Cholestasis (LIV01, 10 Genes)

ABCB11, ABCB4, ATP8B1, KIF12, NR1H4, MYO5B, TJP2, USP53, VPS33B, ZFYVE19

More information on LIV01

Progressive familial intrahepatic cholestasis, or short PFIC, is an umbrella term for heterogeneous liver diseases with an impaired outflow of bile. As a result, bile components accumulate in liver and blood, leading to liver fibrosis over time and subsequent liver cirrhosis (often in the first decade of life), which leaves a liver transplant as the only treatment option. The impaired bile outflow is usually caused by a defect in one of the transport proteins embedded in the hepatocyte membrane, leading to different forms of PFIC that are all based on autosomal recessive inheritance. With a prevalence of 1:50-10,000, PFIC is one of the most common liver diseases. Phenotypically, the different PFIC types overlap to some extent so that they can often only be differentiated by means of immunostaining or genetically. However, the onset of the disease (from birth to early adulthood) and the severity of the disease vary, and different combinations of important liver function parameters such as GGT, alkaline phosphatase, or bilirubin are usually elevated or normal. Furthermore, non-specific symptoms such as severe itching, recurrent or permanent jaundice, hepatomegaly, malabsorption (of fats/fat-soluble vitamins), or failure to thrive can occur, and some PFIC forms are also associated with pancreatitis or sensorineural hearing loss (Amendola and Squires, updated 2023, PMID: 36108118, GeneReviews; Siddiqi and Tadi, updated 2023, PMID: 32644743, StatPearls).

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Lysosomal Storage Disorders with Liver Involvement (LIV06, 5 Genes)

GBA, LIPA, NPC1, NPC2, SMPD1

More information on LIV06

Lysosomal storage disorders with liver involvement are metabolic diseases that are caused by defective or inadequate function of the lysosomes. These cell organelles are responsible for the metabolization of exogenous substances and prevent their toxic accumulation. Depending on the degraded substance class, a distinction is therefore made between:

Lipidoses: defect of the lysosomal lipases, accumulation of lipids
Mucopolysaccharidoses: defect of the lysosomal glycosidases, accumulation of proteoglycans
Oligosaccharidosis: defect of the lysosomal oligosaccharidases, accumulation of glycoproteins
Mucolipidoses: a combination of the symptoms of mucopolysaccharidoses and lipidoses

Accordingly, there is a broad spectrum of symptoms that range from bone pain, reduced physical fitness, eye abnormalities, increased susceptibility to infections, diarrhea, and vomiting to neurological symptoms such as ataxia, gaze palsy, and dystonia, a reduction in platelets/erythrocytes, failure to thrive and progressive loss of cognitive abilities. In severe cases and without treatment, the disease can be fatal in early childhood. In addition to an increase in the size of the liver and spleen (hepatosplenomegaly), calcified adrenal glands can also occur. The gene panel LIV-06 covers the lysosomal storage diseases Morbus Gaucher (GBA1), Wolman disease (LIPA), and the various types of Niemann-Pick disease (NPC1/NPC2/SMPD1). All of these diseases follow an autosomal recessive mode of inheritance, and early onset is mainly correlated with more severe symptoms, which are dependent on residual enzyme activity. Therefore, the diagnosis can often be made biochemically by measuring relevant enzyme activities, followed by genetic diagnostics for confirmation. Treatment usually involves regular enzyme replacement therapy via intravenous infusions or, if necessary, a bone marrow or stem cell transplant (Rajkumar and Dumpa, updated 2023, PMID: 33085417, StatPearls; Uribe-Carretero et al., 2024, PMID: 38248465).

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Cholestasis (LIV10, 42 Genes)

ABCB11, ABCB4, ABCC2, ACOX2, ADK, AKR1D1, AMACR, ATP7B, ATP8B1, BAAT, CCDC115, CFTR, CLDN1, CYP27A1, CYP7B1, DCDC2, DGUOK, FAH, FOCAD, GALE, GALT, GIMAP5, HSD3B7, JAG1, KIF12, MPV17, MYO5B, NBAS, NOTCH2, NR1H4, PKHD1, POLG, RINT1, SLC25A13, TJP2, TRMU, TULP3, USP53, VIPAS39, VPS33B, VPS50, ZFYVE19

More information on LIV10

The LIV-10 panel includes all relevant genes associated with cholestasis (see LIV-01), as well as the genes JAG1 and NOTCH2, which are specific for autosomal dominant Alagille syndrome. The liver involvement in Alagille syndrome is characterized by an inborn malformation of the bile ducts or a reduction in their number. The resulting cholestasis leads to inflammation and scarring and, ultimately, to liver cirrhosis. However, the disease course is usually mild and often stabilizes by the age of 4 to 10 years, but life-threatening complications can also occur. Symptoms can include severe itching, recurrent or permanent jaundice, increased bilirubin and cholesterol levels, failure to thrive, and fatty deposits in the skin. Malformations of the spine, iris, kidneys, heart, and face have also been described. Diagnosis is made through laboratory tests, imaging procedures, a liver biopsy, or a genetic analysis to differentiate between type 1 (ALGS1, gene JAG1) and type 2 (ALGS2, gene NOTCH2). Treatment is usually performed by medication, but a special diet or surgery can also improve bile excretion and nutrient supply and help manage pain. However, severe cases require a liver transplant (Spinner et al., updated 2024, PMID: 20301450, GeneReviews).

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Hemochromatosis (Hemochromatosis)

HFE (p.Cys282Tyr)

Alpha-1-Antitrypsin Deficiency (Alpha-1-Antitrypsin Deficiency)

SERPINA1 (common pathogenic alleles)

Gene Directory – Panel for Liver Diseases

ABCB11, ABCB4, ABCC2, ACOX2, ADK, AKR1D1, AMACR, ATP7B, ATP8B1, BAAT, CCDC115, CFTR, CLDN1, CYP27A1, CYP7B1, DCDC2, DGUOK, FAH, FOCAD, GALE, GALT, GBA1, GIMAP5, HSD3B7, JAG1, KIF12, LIPA, MPV17, MYO5B, NBAS, NOTCH2, NPC1, NPC2, NR1H4, PKHD1, POLG, RINT1, SLC25A13, SMPD1, TJP2, TRMU, TULP3, USP53, VIPAS39, VPS33B, VPS50, ZFYVE19

Additional Services

HLA-Typing (HLA01)

HLA class I (Gene A, B, C) and HLA class II (Gene DPA1, DPB1, DQA1, DQB1, DRB1, DRB3, DRB4, DRB5)

ACMG Genes

Genetic variation may sometimes be identified, which does not fit within the scope of the requested genetic analysis (so-called secondary findings). The reporting of these variants is limited to pathogenic alterations (ACMG classes 4 and 5) within selected genes, for which a treatment or course of action exists for you or your family (according to the current guidelines of the American College of Medical Genetics and Genomics).

Details on genes and associated diseases can be found here

Pharmacogenetics

Pharmacogenetic analysis detects genetic changes that affect the effectiveness of drugs. Genetic variants that affect proteins responsible for the metabolism of substances can significantly change their tolerance and efficacy. These drugs include, among others, antidepressants, pain relievers, neuroleptics, chemotherapeutics, AIDS drugs, thrombosis drugs, anesthetics, beta-blockers, or statins.

The reduced activity of a specific enzyme can lead to an increased drug level in the standard dosage, which is often associated with undesirable side effects. With drugs that are only activated by metabolism, the therapeutic effect can be completely absent. Likewise, due to the resulting increased rate of degradation of the medicinal substance, an increased enzyme activity leads to inadequate effectiveness of the therapy.

The pharmacogenetics option analyzes known variants in twenty-one genes involved in the metabolism of drugs. If specific gene variants occur, the treating doctor can adapt the therapy individually. The pharmacogenetic analysis can minimize serious side effects and helps to avoid failure of the treatment.

Details on genes and more infomation can be found here