Variant Synonymizer: Platform to identify mutations defined in different ways is available now!
Over 2,000 gene–disease validation summaries are now available—no login required!
In a Spanish family with cold‐induced recurrent fever, urticarial rash, papular eruptions, and digital oedema, next‐generation sequencing identified a heterozygous PSTPIP1 variant, c.657A>T (p.Gln219His), in one affected sister and her asymptomatic father (PMID:35383566). Despite elevated cytokine production in monocyte assays, segregation analysis did not support PSTPIP1 c.657A>T (p.Gln219His) as causative, and concurrent identification of NLRC4 p.Leu339Pro with perfect segregation suggests an alternative genetic driver.
No additional unrelated probands, families, or recurrent PSTPIP1 variants have been reported in MONDO_0019751–diagnosed individuals. Functional studies have not demonstrated a direct pathogenic role for PSTPIP1 p.Gln219His in autoinflammatory syndrome, and experimental concordance is lacking. Taken together, the current evidence conflicts with a primary role for PSTPIP1 in this autoinflammatory phenotype.
Key Take-home: PSTPIP1 c.657A>T (p.Gln219His) lacks segregation and functional validation for MONDO_0019751, underscoring the need for further genetic and mechanistic studies to define its clinical relevance.
Gene–Disease AssociationDisputedSingle-family report with a non-segregating PSTPIP1 variant and an alternative NLRC4 variant implicated. Genetic EvidenceLimitedc.657A>T (p.Gln219His) detected in one proband and unaffected father; no segregation ([PMID:35383566]). Functional EvidenceLimitedNo functional data directly linking PSTPIP1 p.Gln219His to MONDO_0019751; assays point to NLRC4 variant instead. |