The Hyper IgM Foundation Blog 

NEW YORK, New York — The Hyper IgM Foundation is proud to announce the awarding of a $25,000 research grant to Dr. Rui Yang at Baylor College of Medicine and Texas Children’s Hospital. This seed funding will support a vital diagnostic initiative titled “An Atlas of Variant Effects in CD40 and CD40LG,” aimed at eliminating uncertainty in genetic testing and expediting definitive diagnoses for children and families affected by Hyper IgM Syndrome.

Although next-generation sequencing is now standard practice for diagnosing Hyper IgM, patients and clinicians frequently face a major diagnostic hurdle: variants of uncertain significance (VUS). Approximately 34% of variants in CD40LG (which causes X-linked Hyper IgM) and over 80% of variants in CD40 (which causes HIGM type 3) currently lack clear functional interpretation. These ambiguous test results leave families in diagnostic limbo, delaying critical, life-saving interventions such as stem cell transplantation.

Dr. Yang’s project addresses this gap by creating a comprehensive “functional map” of every possible single-nucleotide variant in CD40LG and CD40. Utilizing a high-throughput laboratory framework called a Multiplexed Assay of Variant Effects (MAVE) paired with a specialized “landing pad” cell system, the research team will systematically test all coding mutations—both known and theoretical—for their effects on protein expression, molecular binding, and downstream immune signaling.

Hyper IgM Foundation President Akiva Zablocki, MPH, stated:

“When a family is facing a potential Hyper IgM diagnosis, every day spent waiting for answers is crucial. This grant reflects the Foundation’s dedication to removing diagnostic roadblocks. By funding Dr. Yang’s work to construct an open-access functional atlas, we are equipping doctors worldwide with the data they need to turn ambiguous genetic test results into clear, actionable treatment plans—helping patients get access to curative therapies without delay.”

The one-year grant period, running from July 1, 2026, to June 30, 2027, will directly support research expenses to map variant effects and validate them against clinical databases. Importantly, the project culminates in establishing a free, publicly accessible online portal tailored for clinicians, genetic counselors, researchers, and families. This tool will allow anyone to search a specific genetic variant in CD40LG or CD40 and immediately ascertain whether it is disease-causing or benign.

Hyper IgM Syndromes are rare, life-threatening primary immunodeficiencies that severely compromise the immune system’s ability to produce protective antibodies, leaving patients highly vulnerable to severe recurrent infections. The Hyper IgM Foundation’s investment in Baylor College of Medicine reflects strategic funding designed to turn complex genomic data into immediate clinical utility for the patient community.

About the Hyper IgM Foundation

The Hyper IgM Foundation’s mission is to improve the treatment, quality of life, and long-term outlook for children and adults living with Hyper IgM Syndrome. In addition to funding cutting-edge research, the Foundation connects families affected by Hyper IgM with vital education, advocacy, and peer support. Since its inception, the Hyper IgM Foundation has awarded more than $430,000 in research grants to advance the global understanding and cure of this rare immunodeficiency.

To learn more about Hyper IgM Syndrome or to support the Foundation’s ongoing research initiatives, please visit https://hyperigm.org/

For media inquiries or scientific questions about this grant, please contact info@hyperigm.org.