Genomic of CONgenital Sideroblastic Anemias

NCT07459816 | Recruiting

• 1 other identifier: PI2025_843_0155
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Congenital sideroblastic anemias (CSA) are a group of rare disorders characterized by abnormal iron utilization during erythropoiesis, leading to mitochondrial iron overload, the formation of ring sideroblasts, and ineffective erythropoiesis resulting in anemia. Ring sideroblasts are erythroid precursors that contain non-heme iron deposits in their mitochondria, forming a distinctive ring-like pattern around the nucleus. Mitochondria are double membrane organelle provide a large amount of energy for cellular activities, by the process of oxidative phosphorylation (OXPHOS). The role of mitochondria has been well described in erythropoiesis. CSA exhibits clinical heterogeneity, affecting only the erythroid system in some cases, while in others presenting as part of broader syndromic conditions. Their molecular basis remains imperfectly known, although the development of next- generation sequencing technology brought tremendous advances in the understanding of their genetic features. More than 20 genes have been identified as causative of CSA, with all modes of inheritance observed: X-linked recessive, autosomal dominant, autosomal recessive, pseudo- dominant, and mitochondrial. These genes are typically involved in one of four key mitochondrial pathways: i) Heme biosynthesis (e.g., ALAS2, SLC25A38); ii) Iron-sulfur cluster biosynthesis and transport (e.g., GLRX5, HSPA9, HSCB); iii) tRNA synthesis and maturation (e.g., PUS1, YARS2, LARS2, IARS2, SARS2, MARS1, TRNT1); iv) Mitochondrial respiratory chain synthesis (e.g., NDUFB11). However, in nearly 30% of cases within the French CSA cohort, the underlying genetic cause remains unknown. In these patients with molecularly unexplained whole genome or exome sequencing approaches focusing on genes involved in mitochondrial function and iron metabolism identified several possibly pathogenic variants in CSA patients. These genes were not clearly described as playing a role in erythropoiesis or heme or iron metabolism. We hope to confirm their role in CSA. However, in nearly 30% of cases within the French CSA cohort , the underlying genetic cause remains unknown. The investigators hope to confirm the role in CSA of gene identified with exome sequencing approaches.

Conditions

Anemia; Genetics; Erythropoiesis

Keywords

Anemia; genetics; erythropoiesis

Outcome Measures

Primary Outcomes (2)

• Identification of genetic variants in Congenital sideroblastic anemias

  Variants potentially altering the splicing site

  1 year

• Identification of nonsense and missense genetic variants in Congenital sideroblastic anemias

  Nonsense and missense variants: study of protein expression or protein size by Western Blot or protein-protein interactions in blood mononuclear cells

  1 year

Secondary Outcomes (4)

• level of mitochondrial membrane potential

  1 year

• Measurement of mitochondrial Ros production

  1 year

• Measurement of mitochondrial mass

  1 year

• Measurement of erythroid differentiation

  1 year

Study Arms (2)

Congenital sideroblastic anemia

EXPERIMENTAL

Biological: blood redrawal

Patients without Congenital sideroblastic anemia

ACTIVE COMPARATOR

Biological: blood redrawal

Interventions

blood redrawal BIOLOGICAL

Peripheral blood mononuclear cells collected in EDTA (7 mL) and ACD tube (7 mL) during a routine sample collection for patients

Congenital sideroblastic anemia; Patients without Congenital sideroblastic anemia

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient with unexplained congenital sideroblastic anemia on the molecular side with the gene panels used routinely
• Patients already identified by exome sequencing approach carrying bi-allelic variants of candidate genes of the mitochondrial respiratory pathway.
• Patients meeting the same criteria who will be identified prospectively over the next 12 months

Sponsors & Collaborators

• Centre Hospitalier Universitaire, Amiens: lead

Study Sites (1)

Amiens University Hospital

Amiens, 80054, France

RECRUITING

MeSH Terms

Conditions

Anemia

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Ophélie Evrard, MD

CONTACT

33+322835127; evrard.ophelie@chu-amiens.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: March 10, 2026
• Study Start: October 28, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)