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Candidate Gene for Hyperferritinemia

NCT05659017 · Status: RECRUITING · Type: OBSERVATIONAL · Enrollment: 100

Last updated 2024-01-05

No results posted yet for this study

Summary

Ferritin is a ubiquitous protein capable of storing iron in the cell cytosol. Stored iron is released and made available for cellular needs by the degradation of ferritin itself. Small amounts of ferritin are present in the blood and consist of ferritin L, a glycosylated form of L called ferritin G, and trace amounts of ferritin H. It is secreted mainly by macrophages, hepatocytes, and lymphoid cells, but most aspects of its secretion remain not fully elucidated. Serum ferritin has broad clinical utility primarily as an indicator of iron stores, so low values of serum ferritin are indicative of a deficient state and high values of iron overload. However, the causes of increased serum ferritin are numerous, in many cases serum ferritin is increased disproportionately to iron stores such as in acute and chronic liver disease, infectious and inflammatory states, metabolic disorders, and high alcohol intake that are frequently observed in the clinical setting. Therefore, the diagnosis of hyperferritinemia requires a careful strategy including personal and family history, biochemical, instrumental, and targeted genetic testing. In fact, there are rare forms of genetically determined hyperferritinemia not associated with iron overload, such as hereditary cataract hyperferritinemia syndrome (HHCS) due to mutations in the Iron responsive Element (IRE) located in the 5' untranslated region of the FTL gene. More recently, a second dominant form of genetic hyperferritinemia without iron overload or cataract (benign hyperferritinemia) has been identified.

Preliminary results obtained so far have made it possible, through WES analysis, to identify the involvement of the STAB1 gene, which was found to be mutated in the studied subjects in whom reduced serum ferritin glycosylation and reduced plasma concentration of the protein itself were observed. It is therefore deemed necessary to proceed with the assay of glycosylated ferritin and the protein encoded by the gene to assess its sensitivity and specificity as a predictive test before performing the genetic analysis of STAB1. To achieve this goal, patients with undefined hyperferritinemia afferent to the SSD Rare Diseases of the IRCCS San Gerardo Foundation in whom to perform glycosylated ferritin and STAB1 protein assay in parallel with STAB1 sequencing will be evaluated. Similar investigations will be performed in a control group consisting of cases of hyperferritinemia due to genetically determined iron overload.

Conditions

  • Hyperferritinemia

Interventions

GENETIC

Genetic analysis

The DNA will then be analyzed with a custom panel designed ad hoc to study the candidate gene by Next Generation Sequencing according to the protocols of the supplier of the kit.

Sponsors & Collaborators

  • University of Milano Bicocca

    lead OTHER

Eligibility

Min Age
18 Years
Max Age
80 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2022-06-06
Primary Completion
2024-01-03
Completion
2024-09-30

Countries

  • Italy

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05659017 on ClinicalTrials.gov