Figure 2.
Identification of biallelic STAT2 p.R148Q variants in and their population genetic characterization. (A) Familial segregation of the c.443G>A STAT2 variant in P1 and P2 patients and their families. Double horizontal lines indicate consanguinity; a black square represents affected patients (P1, P2); a dotted square indicates a suspected individual with a phenotype similar to the patient but unknown genetic status (E?); a diagonal slash indicates a deceased individual; a circle represents a female and a square represents a male; M, mutant; WT, wild type. (B) Principal component analysis (PCA) of WES data of the patients (P1, P2, and P3), our in-house database, and samples from the 1,000 Genomes database. (C) Expression of ISG mRNA in whole blood collected from P1 (n = 1) and healthy donors (HD) (n = 4). (D) Shared haplotype around the c.443G>A STAT2 variant of patients (P1, P2, and P3). The distance from the mutation is represented on the x-axis. Long continuous stretches of homozygosity were observed around the gene, consistent with its recessive mode of inheritance, and haplotypes were unambiguously derived from genotypes. The dbSNP reference numbers of the first and last unambiguous variants within the haplotype are reported for each carrier. Refer to the image caption for details. Panel A shows pedigree diagrams of two families illustrating segregation of the STAT2 c.443G>A, p.R148Q variant, with affected individuals, carriers, consanguinity, and deceased family members indicated using standard pedigree symbols. Panel B shows a principal component analysis (PCA) scatter plot of whole-exome sequencing data comparing patients P1, P2, and P3 with reference populations including African, American, Asian, European, Middle Eastern, and North African groups. Panel C shows bar graphs comparing interferon-stimulated gene (ISG) mRNA expression levels in whole blood from healthy donors (HD) and patient P1 for IFI27, IFI44L, IFIT1, ISG15, RSAD2, and SIGLEC1. Panel D shows shared haplotype maps surrounding the STAT2 c.443G>A variant in patients P1, P2, and P3, with genomic distances, homozygous regions, and flanking  Single Nucleotide Polymorphism Database (dbSNP) markers represented along the chromosomal region.

Identification of biallelic STAT2 p.R148Q variants in and their population genetic characterization. (A) Familial segregation of the c.443G>A STAT2 variant in P1 and P2 patients and their families. Double horizontal lines indicate consanguinity; a black square represents affected patients (P1, P2); a dotted square indicates a suspected individual with a phenotype similar to the patient but unknown genetic status (E?); a diagonal slash indicates a deceased individual; a circle represents a female and a square represents a male; M, mutant; WT, wild type. (B) Principal component analysis (PCA) of WES data of the patients (P1, P2, and P3), our in-house database, and samples from the 1,000 Genomes database. (C) Expression of ISG mRNA in whole blood collected from P1 (n = 1) and healthy donors (HD) (n = 4). (D) Shared haplotype around the c.443G>A STAT2 variant of patients (P1, P2, and P3). The distance from the mutation is represented on the x-axis. Long continuous stretches of homozygosity were observed around the gene, consistent with its recessive mode of inheritance, and haplotypes were unambiguously derived from genotypes. The dbSNP reference numbers of the first and last unambiguous variants within the haplotype are reported for each carrier.

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