Prevalence of Genetic Mutations in Patients With Neuropathy Associated With Anti-Myelin-associated Glycoprotein (MAG) Antibodies

Neuropathy Demyelinating Clinical Trial

— GENOMAG  

Official title:

Observational Study of the Prevalence of Some Genetic Mutations in Patients With Neuropathy Associated With Anti-Myelin-associated Glycoprotein (MAG) Antibodies.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03268161
• Other study ID #: 35RC15_3018
• Status: Completed
• Phase: N/A
• First received: August 29, 2017
• Last updated: February 26, 2018
• Start date: October 21, 2015
• Est. completion date: November 10, 2017

Study information

• Verified date: February 2018
• Source: Rennes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Anti-MAG (Myelin Associated Glycoprotein) neuropathy is related to clonal B lymphocyte proliferation producing an monoclonal immunoglobulin (IgM) with anti-MAG activity. IgM may be a reflection of malignant lymphoproliferative syndrome (Waldenström disease) or, more often, monoclonal gammopathy of unknown significance.

The anti-MAG antibody has a direct toxicity on the myelin sheath of the peripheral nervous system responsible for a length-dependent demyelinating polyneuropathy. Clinically, this results in a sensitive, ataxic predominant polyneuropathy in the lower limbs, sometimes associated with a tremor of attitude and action tremor of the upper limbs.

Clonal B cells at the origin of IgM production may have acquired mutations affecting MYD88 (MYD88 L265P mutation) and CXCR4 (Whim-like CXCR4 mutation). The prevalence of the MYD88 L265P mutation is estimated to be 50% in monoclonal gammopathies of undetermined significance and more than 80% in Waldenström disease. CXCR4 Whim-like mutations are found in 40% of patients with Waldenström's disease.

No studies have reported the prevalence of these mutations in patients with anti-MAG neuropathies.

Description:

This is a retrospective observational study in patients with anti-MAG neuropathy. Mutational analysis will be performed for patients with a medullary or blood sample stored in a bio-bank during lymphocyte phenotyping. This phenotyping was carried out most often in search of a malignant haemopathy associated with the monoclonal peak. No new samples were taken from the patient (blood or spinal cord).

Immunoglobulin gene rearrangement of the clonal B cells are also assessed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: November 10, 2017
• Est. primary completion date: November 10, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with anti-MAG neuropathy

• Blood and/or bone marrow samples available in bio-bank

• Given informed consent

Exclusion criterion

• Participation refusal

Related Conditions & MeSH terms

• Neuropathy Demyelinating
• Peripheral Nervous System Diseases

Intervention

Diagnostic Test:
• Mutational analysis of clonal B cells
Mutational analysis based on medullary or blood samples stored in a bio-bank during routine lymphocyte phenotyping. Mutations affecting MYD88 (MYD88 L265P mutation), CXCR4 (Whim-like CXCR4 mutation) loci are sought.

Locations

Country	Name	City	State
France	Rennes University Hospital	Rennes

Sponsors (1)

Lead Sponsor	Collaborator
Rennes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of MYD88 L265P mutations in anti-MAG neuropathies	Mutational status of MYD88 L265P is assessed using high-throughput sequencing (HTS) and allele specific polymerase chain reaction (AS-PCR)	At inclusion : after the patient's given consent
Primary	Prevalence of CXCR4 Whim-like mutations in anti-MAG neuropathies	Mutational status of CXCR4 is assessed using HTS and AS-PCR	At inclusion : after the patient's given consent
Secondary	Immunoglobulin gene rearrangement	Immunoglobulin gene rearrangements are determined with a multiplex PCR	At inclusion : after the patient's given consent