Case#: P2, 10 year old boy

DiseaseAssertion: APDS

CaseHPOFreeText: presented with recurrent otitis media and sinusitis since his first year of life. He had an adenoidectomy at 3 years of age. He presented with high IgM but normal IgG and IgA serum levels (Table 1). The serum levels of IgG2 (0.23; N: 0.56) and IgG4 (<0.002; N: 0.018) subclasses were low.

CasePreviousTesting: Thus, mutations known to cause APDS1 or APDS2 were searched and excluded by Sanger sequencing

GenotypingMethod: For P2 and P3, a targeted Next-Generation sequencing of a primary immunodeficiencies gene panel including PIK3CD and PIK3R1 was performed

Variant: A heterozygous G to A mutation at position 9775907 (GRCh37; NM_005026.3) in the PIK3CD gene was detected. The mutation leads to an amino acid substitution from glycine to aspartic acid at position 124 (G124D) located in the linker region between the ABD and the RBD at the N-terminal part of p110δ (Figure 1A).

CAID: CA338300460

gnomAD: absent from gnomAD v2.1.1

Case#: P3, 9 year old girl

DiseaseAssertion: APDS

CaseHPOFreeText: presented with growth retardation since 6 months of age (currently −3 SD of height and −2.5 SD of weight). Lymphadenopathy and splenomegaly were noted at the age of 8 years, and adenoidectomy and tonsillectomy were performed. She had decreased IgA but normal IgG and IgM serum levels. Her mother had a similar clinical phenotype and died from Hodgkin lymphoma.

CasePreviousTesting: Thus, mutations known to cause APDS1 or APDS2 were searched and excluded by Sanger sequencing

GenotypingMethod: For P2 and P3, a targeted Next-Generation sequencing of a primary immunodeficiencies gene panel including PIK3CD and PIK3R1 was performed

Variant: A heterozygous G to A mutation at position 9775907 (GRCh37; NM_005026.3) in the PIK3CD gene was detected. The mutation leads to an amino acid substitution from glycine to aspartic acid at position 124 (G124D) located in the linker region between the ABD and the RBD at the N-terminal part of p110δ (Figure 1A).

CAID: CA338300460

gnomAD: absent from gnomAD v2.1.1