Case#: Q.II.1, subject 44. Male. Age of Onset: 10 y.o. Age of evaluation/death: 15 y.o. Origin in UK, Caucasian.

DiseaseAssertion: Lymphoproliferation

FamilyInfo: Not found

CasePresentingHPOs: HP:0001744, HP:0002716, HP:0002783, HP:0000964, HP:0001873

CaseHPOFreeText: Three affected mutation carriers (including patient) died following alloHSCT due to GvHD. Patient received transplant due to having Thrombocytopenia and widespread lymphoid hyperplasia despite Rituximab. Patient died four months post transplant due to Acute GvHD Grade IV of the gut. See Table S2.

Lymphocytic or granulomatous organ infiltration - patient's brain was affected. Patient received a biopsy and was found to have B Cell and T Cell infiltration. Vaccination response - Tetanus, Pneumococcal vaccination. Respiratory tract involvement, GLILD, Cytopenia, Splenectomy, Autoimmune cytopenia, ITP, Neurological involvement, Dermatological involvement, Coombs.

CaseNotHPOs: large phenotype table with unreported symptoms in table S1

CaseNotHPOFreeText: Patient was checked for a number of additional phenotypes but none were identified. Please see Supplementary table S1 for details.

CasePreviousTesting: Genome-wide methods were not used (sequencing of CTLA4 was performed, but no reference made to other genes tested). Some families received whole-exome sequencing but we are unsure if this patient was included.

GenotypingMethod: The authors imply that they sequenced the four exons of CTLA4.

PreviouslyPublished: Yes, Slatter, et al. PMID: 27102614

Variant: NM_005214.5:c.529T>G

ClinVarID: N/A

CAID: CA350139018

gnomAD: Not found

SupplementalData: extensive data in S1

Note: Not functionally tested using transendocytosis

Case#: OO.II.1, subject 95. Male. Age of Onset: 18 y.o. Age of evaluation: 24 y.o. Origin in Germany, Caucasian.

DiseaseAssertion: CVID

FamilyInfo: Patient was included in group of families who had a documented mutation at Exon: 2 and AA Position: 75. Mutations were: p.R75W (c.223C>T) and p.R75Q (c.224G>A). Family groups were: Family E, Family X, Family JJ, Family UU; Family OO.

CasePresentingHPOs: ORPHA:1572 (CVID), HP:0004313 (Hypogammaglobulinemia), HP:0004315 (Low IgG), HP:0001744 (Splenomegaly), HP:0200117 (Recurrent upper and lower respiratory tract infections), HP:0002090 (Pneumonia), HP:0002110 (Bronchiectasis), HP:0002726 (Recurrent Staphylococcus aureus infections), OMIM:188030 (Immune thrombocytopenic purpura/ITP)

CaseHPOFreeText: Respiratory involvement, Low IgM, Low IgA, Lymphoproliferation, Respiratory tract involvement, GLILD, Cytopenia, Autoimmune cytopenia

Bacterial infection: Hemophilus influenzae

Lymphocytic or granulomatous organ infiltration - Lung.

CaseNotHPOs: large phenotype table with unreported symptoms in table S1

CaseNotHPOFreeText: Patient was checked for a number of additional phenotypes but none were identified. Please see Supplementary table S1 for details.

CasePreviousTesting: Genome-wide methods were not used (sequencing of CTLA4 was performed, but no reference made to other genes tested). Some families received whole-exome sequencing but we are unsure if this patient was included.

GenotypingMethod: The authors imply that they sequenced the four exons of CTLA4.

PreviouslyPublished: N/A

Variant: NM_005214.5:c.224G>A

ClinVarID: 943305

CAID: CA350138321

gnomAD: Not found

SupplementalData: extensive data in S1

Note: Functionally tested using transendocytosis

Case#: YY.II.1, subject 127. Female. Age of Onset: 3 y.o. Age of evaluation: 14 y.o. Origin in Germany, Caucasian.

DiseaseAssertion: Gastrointestinal involvement

FamilyInfo: None found

CasePresentingHPOs: HP:0001510 (Growth retardation), HP:0001744 (Splenomegaly), HP:0002240 (Hepatomegaly), HP:0002716 (Lymphadenopathy), HP:0200117 (Recurrent upper and lower respiratory tract infections), HP:0002726 (Recurrent Staphylococcus aureus infections), HP:0020114 (Persistent human papillomavirus infection/HPV), HP:0002014 (Diarrhea), HP:0002242 (Enteropathy), HP:0100280 (Crohn's disease), HP:0001047 (Atopic dermatitis), HP:0000964 (Eczema), HP:0200043 (Warts)

CaseHPOFreeText: Lymphoproliferation, Respiratory tract involvement, Dermatological involvement, Liver involvement

Lymphocytic or granulomatous organ infiltration - Liver and gut

Vaccination response - Tetanus, Diphtheria and Pneumococcal

CaseNotHPOs: large phenotype table with unreported symptoms in table S1

CaseNotHPOFreeText: Patient was checked for a number of additional phenotypes but none were identified. Please see Supplementary table S1 for details.

CasePreviousTesting: Genome-wide methods were not used (sequencing of CTLA4 was performed, but no reference made to other genes tested). Some families received whole-exome sequencing but we are unsure if this patient was included.

GenotypingMethod: The authors imply that they sequenced the four exons of CTLA4.

PreviouslyPublished: N/A

Variant: NM_005214.5:c.326G>A

ClinVarID: 542071

CAID: CA2067088

gnomAD: 2:204735525 G / A

SupplementalData: extensive data in S1

Note: Functionally tested using transendocytosis