case_images: PMC11381395_01
case_images: Summary of findings of families 1, 2, and 3. (A) Pedigree of the families, including the coding change and the specific amino acid substitution. Black solid symbols represent affected subjects, the open symbol represents an unaffected subject, the dotted symbol represents a subject carrying a postzygotic mutation, squares represent male subjects, and circles represent female subjects. (B) Detection of PIK3CD pathogenic variant in exome, Sanger, genome, or targeted deep sequencing in families 1, 2, and 3. (C) Genomic information of pathogenic PIK3CD variants in families 1, 2, and 3.
case_images: fimmu-15-1451212-g001.jpg
case_images: PMC11381395_03_fimmu-15-1451212-g001.jpg
case_images: f1
case_images: PIK3CD in two affected siblings (II.1 and II.2) born to non-consanguineous parents (I.1 and I.2) of reportedly diverse genomic ancestry ( Figure 1C ). Their mother and father are both apparently unaffected with no major health issues. Through exome sequencing of genomic DNA extracted from whole blood from the proband (II.1) and the sibling (II.2), we detected the PIK3CD variant in 27/43 reads (63% VAF) and 19/31 reads (61% VAF), respectively ( Figure 1B ).
case_images: PMC11381395_02
case_images: Summary of findings of families 1, 2, and 3. (A) Pedigree of the families, including the coding change and the specific amino acid substitution. Black solid symbols represent affected subjects, the open symbol represents an unaffected subject, the dotted symbol represents a subject carrying a postzygotic mutation, squares represent male subjects, and circles represent female subjects. (B) Detection of PIK3CD pathogenic variant in exome, Sanger, genome, or targeted deep sequencing in families 1, 2, and 3. (C) Genomic information of pathogenic PIK3CD variants in families 1, 2, and 3.
case_images: fimmu-15-1451212-g001.jpg
case_images: PMC11381395_03_fimmu-15-1451212-g001.jpg
case_images: f1
case_images: PIK3CD in two affected siblings (II.1 and II.2) born to non-consanguineous parents (I.1 and I.2) of reportedly diverse genomic ancestry ( Figure 1C ). Their mother and father are both apparently unaffected with no major health issues. Through exome sequencing of genomic DNA extracted from whole blood from the proband (II.1) and the sibling (II.2), we detected the PIK3CD variant in 27/43 reads (63% VAF) and 19/31 reads (61% VAF), respectively ( Figure 1B ).
case_images: PMC11381395_03
case_images: Summary of findings of families 1, 2, and 3. (A) Pedigree of the families, including the coding change and the specific amino acid substitution. Black solid symbols represent affected subjects, the open symbol represents an unaffected subject, the dotted symbol represents a subject carrying a postzygotic mutation, squares represent male subjects, and circles represent female subjects. (B) Detection of PIK3CD pathogenic variant in exome, Sanger, genome, or targeted deep sequencing in families 1, 2, and 3. (C) Genomic information of pathogenic PIK3CD variants in families 1, 2, and 3.
case_images: fimmu-15-1451212-g001.jpg
case_images: PMC11381395_03_fimmu-15-1451212-g001.jpg
case_images: f1
case_images: PIK3CD in two affected siblings (II.1 and II.2) born to non-consanguineous parents (I.1 and I.2) of reportedly diverse genomic ancestry ( Figure 1C ). Their mother and father are both apparently unaffected with no major health issues. Through exome sequencing of genomic DNA extracted from whole blood from the proband (II.1) and the sibling (II.2), we detected the PIK3CD variant in 27/43 reads (63% VAF) and 19/31 reads (61% VAF), respectively ( Figure 1B ).
case_images: Summary of Long Read Whole Genome Sequencing analysis in Family 3. (A) Variants near the pathogenic c.3061G>A (p.Glu1021Lys) PIK3CD variant (chr1:9726972G>A; highlighted in red box) in Integrative Genomics Viewer (https://www.igv.org) for Daughter, Father, Mother, and Son from top to bottom panel. Variants surrounding pathogenic variant are highlighted in green boxes. (B) Phased variants near the pathogenic c.3061G>A (p.Glu1021Lys) PIK3CD variant (chr1:9726972G>A; in bold). Shared paternal haplotype is highlighted in blue.
case_images: fimmu-15-1451212-g002.jpg
case_images: PMC11381395_03_fimmu-15-1451212-g002.jpg
case_images: f2
case_images: Haplotype analyses of chromosomal regions surrounding the pathogenic allele showed that the pathogenic variant in PIK3CD resides on the paternal allele in both affected children ( Figure 2 ) ( Supplementary Methods ).