Genetic Analysis of Patients with Two Different Types of Hyper IgM Syndrome

ABSTRACT

Background: Hyper IgM Syndrome (HIGM) is a rare primary immunodeficiency in which impairment of class switching recombination (CSR) and somatic hyper-mutation (SHM) leads to recurrent infections.

Objectives: The aim of this study is to report the clinical and genetic features of six Iranian HIGM patients.

Methods: Six patients, who suspected to have HIGM based on two clinical findings, including recurrent infections and low levels of IgG and IgA and normal or elevated levels of IgM, were entered this study to undergo genetic studies. Sanger sequencing was applied to detect pathogenic mutations in CD40L and AID genes causing two most common forms of HIGM, which known as HIGM type 1 and 2, respectively.

Results: All patients who entered the study were males from unrelated families with a median age of 3.8 years. The most frequent clinical manifestation was recurrent pneumonia. Genetic studies of the patients revealed six different mutations, including five mutations in CD40L besides one mutation in AID. Two mutations in CD40L (p.F31fsX5 and p.C84S) were novel and three mutations (p. G219R, p.D62fsX18, and p.Q186X) have been previously reported. The mutation found in AID (p.E122X) was also previously described.

Conclusion: The study results may provide valuable information for prenatal diagnosis and also for genetic counseling especially for those who have a history of primary immunodeficiency in their family.

KEYWORDS:

• AID
• CD40L
• HIGM
• mutations

Acknowledgments

This research was supported by IAARI, Tehran University of Medical Sciences. We would like to acknowledge Ms. Soosan Nabiloudeshiry for her valuable contribution to this manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Immunology, Asthma & Allergy Research Institute, Tehran University of Medical Sciences.