Hyper-immunoglobulin M syndrome type 3 with normal CD40 cell surface expression.

Area of Science:

• Immunology
• Genetics
• Molecular Biology

Background:

• Autosomal recessive Hyper-IgM syndrome type 3 (HIGM3) is linked to CD40 gene mutations.
• Previous cases showed absent surface CD40 on B lymphocytes via flow cytometry.
• Clinical signs include recurrent infections and specific immunoglobulin level abnormalities.

Observation:

• Two siblings with HIGM3 presented with a novel homozygous four-nucleotide deletion in the CD40 gene.
• This deletion included the stop codon, potentially leading to an altered protein.
• Unlike previous reports, these patients exhibited normal CD40 expression on their B lymphocytes.

Findings:

• The identified CD40 mutation, despite normal surface protein expression, caused HIGM3.
• Clinical and immunological profiles were consistent with previously described HIGM3 patients.
• This highlights a discrepancy between genetic mutation and protein expression in some HIGM3 cases.

Implications:

• CD40 gene mutation analysis is essential for diagnosing HIGM3.
• Relying solely on flow cytometry for CD40 expression can lead to missed diagnoses.
• Further research is needed to understand the functional impact of CD40 mutations with normal protein expression.