X-linked Moesin Associated Immunodeficiency

Official title

Etude Multicentrique Internationale rétrospective Des Patients Atteints de déficit Immunitaire associé à la moésine lié au Chromosome X (X Maid Pour X-linked Moesin Associated Immunodeficiency)

Overview

Moesin deficiency was initially described in 7 male participants aged 4 to 69 years and is characterized by lymphopenia of the 3 lineages and moderate neutropenia. Genetically, 6 out of 7 participants had the same missense mutation in the moesin gene located on the X chromosome. The 7th patient has a mutation leading to the premature introduction of a STOP codon into the protein.Clinically the 7 participants with X-linked moesin-associated immunodeficiency all presented with recurrent bacterial infections of the respiratory, gastrointestinal or urinary tracts, and some had severe varicella.Therapeutically, in the absence of a molecular diagnosis and due to his SCID-like phenotype, one patient was treated with geno-identical hematopoietic stem cell transplantation . The remaining are untreated or treated with immunoglobulin substitution and/or prophylactic antibiotics. Since this study, the moesin gene has been integrated into DNA chips used for the molecular diagnosis of immune deficiencies in several countries. Physicians in Canada, the United States, Japan, South Africa and Europe have contacted us with a total of 16 known participants to date. Because of their very low severe, uncontrolled CMV infection and the absence of treatment recommendations, two 2 American participants were treated with allogeneic transplantation with severe post-transplant complications (1), and one of the participants died as a result of the transplant. Management of XMAID participants therefore varies widely from country to country, depending on age at diagnosis and clinical picture. It ranges from no treatment treatment (associated with recurrent infections and skin manifestations), IgIv substitution and/or antibiotic prophylaxis antibiotic prophylaxis, with low toxicity and apparent efficacy, and allogeneic transplantation, with all the risks risks involved (graft-related toxicity, graft versus host, disease, rejection, risk of infection). The Investigators therefore feel it is important to review the diagnosis, clinical presentation and management of X-MAID participants. The study the investigator propose will enable to understand the presentation of X-MAID participants, establish guidelines and provide the best treatment for each patient according to his or her clinical picture

Detailed description

Since this study, the moesin gene has been integrated into DNA chips used for the molecular diagnosis of immune deficiencies in several countries. Physicians in Canada, the United States, Japan, South Africa and Europe have contacted us with a total of 16 known participants to date. Because of their very low severe, uncontrolled CMV infection and the absence of treatment recommendations, two 2 American participants were treated with allogeneic transplantation with severe post-transplant complications (1), and one of the participants died as a result of the transplant. Management of XMAID participants therefore varies widely from country to country, depending on age at diagnosis and clinical picture. It ranges from no treatment treatment (associated with recurrent infections and skin manifestations), IgIv substitution and/or antibiotic prophylaxis antibiotic prophylaxis, with low toxicity and apparent efficacy, and allogeneic transplantation, with all the risks risks involved (graft-related toxicity, graft versus host, disease, rejection, risk of infection). The investigators therefore feel it is important to review the diagnosis, clinical presentation and management of X-MAID participants. The study the investigators propose will enable to understand the presentation of X-MAID participants, establish guidelines and provide the best treatment for each participant according to his or her clinical picture

Interventions

• Genetic genetic restrospective study
  it is not an interventional study but observational

Primary outcome measures

• The main objective [Time frame: through study completion, and average 3 years]

Secondary outcome measures (1)

• Secondary objectives1 [Time frame: through study completion, and average 3 years]

Eligibility criteria

Inclusion criteria

• Male patient with a mutation in the MOESIN gene (MSN)
• No objection to the collection of personal health data

Exclusion criteria

\-

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Other

Study locations

United States · 3 centers

• National Institutes of Health — Bethesda
• Perelman School of medecine — Philadelphia
• Brown University — Providence

France · 3 centers

• Hôpital Necker — Paris
• CHU Rennes, CNRS UMR 629 — Rennes
• CHU St Etienne Hôpital Nord — Saint-Etienne

Australia · 1 center

• Genomic Research Centre, School of Biomedical Sciences Institute of Health and Biomedical — Brisbane

Belgium · 1 center

• Hôpital Universitaire de la Reine Fabiola — Brussels

Japan · 1 center

• Tokyo Medical and Dental University (TMDU) — Bunkyō City

Netherlands · 1 center

• Departments of Internal Medicine and Immunology — Rotterdam

Identifiers

NCT: NCT06278337 · C19-35

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗