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

Case#: AAA.II.1, subject 130. Male. Age of Onset: 23y.o. Age of evaluation: 46 y.o. Origin in Switzerland, Caucasian.

DiseaseAssertion: Gastrointestinal involvement

FamilyInfo: None found

CasePresentingHPOs: HP:0008207 (Addison's disease), HP:0004313 (Hypogammaglobulinemia), HP:0002720 (Low IgA), HP:0002014 (Diarrhea), HP:0002242 (Enteropathy), HP:0012410 (PRCA/Pure red cell aplasia)

CaseHPOFreeText: Lymphoproliferation, Cytopenia, Autoimmune cytopenia, Endocrinological involvement, Kidney involvement

Lymphocytic or granulomatous organ infiltration of the gut

Thirty-five percent of affected mutation carriers (27/78) were under antibiotic prophylaxis. In one affected mutation carrier (the patient) treatment with vedolizumab (blocking α4β7 integrin) improved colitis, and in the same individual PRCA responded well to cyclosporine A.

IgG levels: no values were available before IVIG or Rituximab

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, Navarini et al. PMID: 27908448

Variant: NM_005214.5:c.257C>T

ClinVarID: 661941

CAID: CA2067080

gnomAD: 2:204735456 C / T

SupplementalData: extensive data in S1

Note: Functionally tested using transendocytosis