Characterization of Two Novel Mutations in the Apob Gene

Study Overview
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Brief Summary
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The pilot study has the target to evaluate the outcomes of two novel mutations in the gene of Apolipoprotein B (ApoB). ApoB is the main part of the low-density lipoprotein (LDL). LDL is the main transporter of cholesterol from the liver to the periphery. The two novel mutations lead to a heavily truncated Apolipoprotein B. Therefore the patients show severely decreased ApoB and LDL-Cholesterol levels. The acquired disease is known as Familial Hypobetalipoproteinemia. Beside the protection from cardiovascular disease due to decreased LDL-Cholesterol, patients tend to show elevated serum aminotransferases, fatty liver and occasional cases of cirrhosis and carcinoma. To elucidate the differences in lipoprotein assembly the investigators aim to characterize the changes due to the mutations in the patients. Family members not carrying the mutations are the control group. The assessment includes lipoprotein fractionation, MRI scans of the liver and a thorough assessment of medical history of all patients to look for potential side effects of the mutation. The only intervention needed for the study is to draw blood samples of every participant. The necessary positive vote from the ethics committee of the Medical University of Innsbruck is given.

Official Title
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Characterization of Two Novel Truncating Mutations in the Apob Gene Leading to Hypobetalipoproteinemia: A Pilot Study

Conditions
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Familial Hypobetalipoproteinaemia - Heterozygous Form, Low-LDL-syndrome

Intervention / Treatment
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* Other: Blood draw


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Full legal age Written Informed Consent Diagnosed hypobetalipoproteinemia Exception of it are the controls Controls have to be family members Exclusion of a truncating mutation in the ApoB gene Exclusion Criteria: No diagnosed hypobetalipoproteinemia No truncating mutation in the Apo B gene Exception of it ar the controls

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients<br>The family members of our two kindreds who carry the truncating mutation in the Apolipoprotein B gene. | Other: Blood draw<br>* Draw venous blood for baseline blood parameters and plasma samples for lipoprotein fractionation.<br>|
| Controls<br>The family members of our two kindreds who are no carriers of the truncating mutation in the Apolipoprotein B gene. | Other: Blood draw<br>* Draw venous blood for baseline blood parameters and plasma samples for lipoprotein fractionation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in lipoprotein profiles | Lipoprotein profiles are measured via Fast Protein Liquid Chromatography in both groups and compared. | 6 months | 
| Differences in amounts of liver fat | Liver fat is non-invasive quantified by MRI scan | 12 months | 
| Differences in HDL-efflux | Compare the results between groups of HDL-efflux assays | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Apolipoprotein B, Cholesterol, Lipoprotein, Metabolism, Steatosis, Cirrhosis, Hepatocellular Carcinoma