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Genomic of CONgenital Sideroblastic Anemias

NCT07459816 · Status: RECRUITING · Phase: NA · Type: INTERVENTIONAL · Enrollment: 20

Last updated 2026-03-11

No results posted yet for this study

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

Interventions

BIOLOGICAL

blood redrawal

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

Sponsors & Collaborators

  • Centre Hospitalier Universitaire, Amiens

    lead OTHER

Study Design

Allocation
NON_RANDOMIZED
Purpose
SCREENING
Masking
NONE
Model
PARALLEL

Eligibility

Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2025-10-28
Primary Completion
2026-11-30
Completion
2026-11-30

Countries

  • France

Study Locations

More Related Trials

Entities

Diseases

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 NCT07459816 on ClinicalTrials.gov