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#: 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