Case#: III.7, an 18-year-old female patient

DiseaseAssertion: immune thrombopenia, autoimmune hemolytic anemia, and Evans syndrome with infections early-onset herpes zoster and chronic Epstein-Barr virus

FamilyInfo: Table 1

CasePresentingHPOs: HP:0001433, HP:0002716

CaseHPOFreeText: severe necrotic dermohypodermitis of left leg caused by Pseudomonas aeruginosa, hypogammaglobulinemia

Variant: c.379T >G variant in CTLA4

GenotypingMethod: high-throughput sequencing

CAID: CA350138665

Case#: Patient 1 (P1) is a 24-year-old Chinese female.

DiseaseAssertion: Patients are asserted to have "CTLA4 haploinsufficiency (CTLA-4 h).

FamilyInfo: The patient's father carries the same CTLA4 variant as the patient but has been asymptomatic. No other family history reported.

CasePresentingHPOs: HP:0031245 (Productive cough), HP:0002105 (Hemoptysis), HP:0001878 (Hemolytic anemia), HP:0006532 (Recurrent pneumonia), HP:0004313 (Decreased circulating immunoglobulin concentration, HP:0033608 (Pulmonary nodule), HP:0002716 (Lymphadenopathy), HP:0001596 (Alpecia),

CaseHPOFreeText: Patient first presented at age 14 with respiratory symptoms. She was hospitalized at age 16 with hemolytic anemia and recurrent pulmonary infections. Lab work showed hypogammaglobinemia. Chest CT showed scattered solid and ground-glass density nodules bilaterally in the lungs, Lung biopsy demonstrated lymphocytic infiltration and siderophages. Treatment with corticosteroids achieved temporary remission, but the patient relapsed with dose tapering. She developed Evans syndrome, alopecia, and skin lesions. Disease stabilized with weekly subcutaneous abatacept (125mg) and the interval was subsequently extended to once every 4 weeks.

CaseNotHPOs: HP:0003493 (Antinuclear antibody positivity), HP:0032230 (Cytoplasmic antineutrophil antibody positivity).

GenotypingMethod: Genotyping was performed by whole exome sequencing.

PreviouslyPublished: No prior article is known to contain information on the same proband.

Variant: The patient is heterozygous for the NM_005214.4(CTLA4):c.155G>T(p.Gly52Val) variant.

ClinVar: 1420586

gnomAD: The variant was not found in gnomAD v4.1.1.

SupplementalData: No supplemental data provided.

Case#: Patient 4 (P4) is a 60-year-old Chinese woman.

DiseaseAssertion: Patients are asserted to have "CTLA4 haploinsufficiency (CTLA-4 h).

FamilyInfo: Patient's daughter is Patient 3 and harbors the same CTLA4 variant.

CasePresentingHPOs: HP:0001954 (Recurrent fever) HP:0011110 (Recurent tonsillitis), HP:0000155 (Oral ulcer), HP:0005558 (Chronic leukemia)

CaseHPOFreeText: Patient's symptoms onset in childhood with recurrent fever and tonsillitis. She experienced recurrent oral ulcers starting around age 50. She was diagnosed with large granular lymphocytic (LGL) leukemia for which she was treated with long-term corticosteroids for three years. She is currently treated with oral cyclosporine.

CaseNotHPOs: HP:0000988 (Skin rash)

CaseNotHPOFreeText: Patient denied history of rash, dry mouth, or dry eyes.

CasePreviousTesting: None reported.

GenotypingMethod: Genotyping was performed via whole exome sequencing.

PreviouslyPublished No prior article is known to contain information on the same proband.

Variant: The patient is heterozygous for the NM_005214.4 CTLA4):c.347T>A (p.Ile116Asn) variant.

ClinVar: 2430678

gnomAD: The variant was not found in gnomAD v4.1.1

SupplementalData: There is no supplemental data.