# Curation of genetic defects causing combined immunodeficiency and infections in children > **NIH NIH U24** · BAYLOR COLLEGE OF MEDICINE · 2021 · $372,321 ## Abstract ABSTRACT Defects in over 400 genes have now been linked to the development of primary immunodeficiency disorders (PIDD). The most severe disorders are known as Combined or Severe Combined Immune Deficiencies (CID or SCID) because they cause a combination of defects in both cellular (T-cell) and humoral (B-cell) compartments of the immune system. As a result, they lead to profound susceptibility to infections early in life and premature death if not treated aggressively with antimicrobials, hematopoietic cell transplant (HCT), gene therapy (GT), or enzyme replacement therapy (ERT). In the U.S., most patients with SCID are now identified by newborn screening (NBS) performed on dried blood spots obtained at birth. Since the specific gene defect present in a patient with SCID has actionable consequences (i.e., dictates the type of aggressive therapy that may be recommended), patients identified by NBS typically undergo early genetic testing using gene panels or exome sequencing. Frequently, genetic testing returns a result of one or more “Variants of Uncertain Significance” or variant(s) in a gene not previously associated with a SCID or CID phenotype. Providers and families are therefore left to try and gather evidence to determine pathogenicity of a particular gene or variant. This effort may delay care or lead to a less-than-optimal choice of therapy. A critical need therefore exists for expert curation of the genetic defects that result in SCID and CID. The objective of this application is to curate the evidence linking specific genes to a SCID or CID phenotype and the evidence for pathogenicity of all variants in the 8 most prevalent genes associated with SCID in infants identified by NBS. This goal will be accomplished with 2 specific aims: 1) Establishment of a Gene Curation Expert Panel (GCEP) to curate evidence linking genes reported to cause SCID or CID to the development of clinical disease according to ClinGen criteria, and 2) Establishment of a Variant Curation Expert Panel (VCEP) to curate evidence for pathogenicity of all variants reported in the 8 most common SCID-associated genes based upon prevalence among infants identified by NBS. Since immune cells can be readily removed from the body for functional testing, a wealth of published data exists from basic immunology studies that may inform this work. This proposal is therefore innovative because it will provide resources to allow GCEP and VCEP panels to link this wealth of published molecular and functional immunology data with clinical and genetic data from published cases and public databases. The work is significant and will have an immediate positive impact because curating evidence about the pathogenicity of genes and gene variants and making it publicly available has immediate actionable consequences that affect timely choice of therapy as described above. The proposed research therefore addresses the mission of the NIH and this RFA by focusing on the establishment of Expert P... ## Key facts - **NIH application ID:** 10173182 - **Project number:** 1U24HD104590-01 - **Recipient organization:** BAYLOR COLLEGE OF MEDICINE - **Principal Investigator:** Ivan Kingyue Chinn - **Activity code:** U24 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2021 - **Award amount:** $372,321 - **Award type:** 1 - **Project period:** 2021-07-01 → 2024-06-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10173182 ## Citation > US National Institutes of Health, RePORTER application 10173182, Curation of genetic defects causing combined immunodeficiency and infections in children (1U24HD104590-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10173182. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*