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.
Name: Mutational analysis of clonal B cells
Description: Mutational status of MYD88 L265P is assessed using high-throughput sequencing (HTS) and allele specific polymerase chain reaction (AS-PCR)
Measure: Prevalence of MYD88 L265P mutations in anti-MAG neuropathies Time: At inclusion : after the patient's given consentDescription: Mutational status of CXCR4 is assessed using HTS and AS-PCR
Measure: Prevalence of CXCR4 Whim-like mutations in anti-MAG neuropathies Time: At inclusion : after the patient's given consentDescription: Immunoglobulin gene rearrangements are determined with a multiplex PCR
Measure: Immunoglobulin gene rearrangement Time: At inclusion : after the patient's given consentCohort
There is one SNP
Clonal B cells at the origin of IgM production may have acquired mutations affecting MYD88 (MYD88 L265P mutation) and CXCR4 (Whim-like CXCR4 mutation). --- L265P ---
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. --- L265P ---
Prevalence of MYD88 L265P mutations in anti-MAG neuropathies. --- L265P ---
Mutational status of MYD88 L265P is assessed using high-throughput sequencing (HTS) and allele specific polymerase chain reaction (AS-PCR). --- L265P ---