Case#: 20-year-old male, Race: White (ancestry unavailable) DiseaseAssertion: The patient is asserted to have "CTLA4 haploinsufficiency" manifesting as aplastic anemia. FamilyInfo: Patient's father has disease variant Case PresentingHPOs: HP:0012378 (Fatigue), HP:0001962 (Palpitations), HP:0002875 (Exertional dyspnea), HP:0001903 (Anemia), HP:0001873 (Thrombocytopenia), HP:0002608 (Celiac disease), HP:0000608 (Macular degeneration), HP:0001876 (pancytopenia), HP:0001915 (aplastic anemia), CaseHPOFreeText: ** Diagnosis at age 20 when patient presented with persistent and profound incapacitating fatigue. Bone marrow biopsy was consistent to aplastic anemia. Table 1 summarizes presenting labs and flow cytometry results. Patient was first treated with high-dose IVIG, cyclosporine, and systemic corticosteroids. He initially responded well, but 6 months into therapy he developed renal impairment and was transitioned to sirolimus. His aplastic anemia relapsed. Patient underwent haploidentical (sibling, variant negative) hematopoietic stem cell transplantation, which was curative. CaseNotHPOs: HP:4000129 (Recent blood transfusion), CaseNotHPOFreeText: N/A CasePreviousTesting: The following studies were negative: Bone marrow chromosome analysis; FISH hybridization for BCR/ABL1, monosomy 5, monosomy 7, trisomy 8, and 20q deletion; myelodysplastic syndrome mutation sequencing. GenotypingMethod: A primary immunodeficiency NGS panel was run (gene content not specified) and identified a paternally inherited heterozygous missense variant in CTLA4. Variant: The patient is heterozygous for the NM_005214.5(CTLA4):c.385T>A (p.Cys129Ser). ClinVar: 1414930 CAID: N/A gnomAD**: This variant was not found in gnomAD v.4.1.0

CTLA-4 functional assay performed to assess impact of NM_005214.5(CTLA4):c.385T>A (p.Cys129Ser) demonstrated impaired expression of CTLA-4. Figure 2 summarizes experimental results.