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Gene: WAS

Green List (high evidence)

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Green List (high evidence)

Definitive gene disease association. Severe immune dysfunction in childhood, complete penetrance but variable phenotype (mildest can be just thrombocytopenia).

Neutropenia, severe congenital is caused by missense variants in the GTPase binding region (L270, S272, I294).

X-linked thrombocytopenia (XLT) is a less severe form of Wiskott-Aldrich syndrome (WAS). Patients are assigned a phenotype score 1-5 (5 being most severe) based on clinical features (PMID: 12040832). Variants that have residual protein expression (“WASP present/reduced”) are associated with mild disease (XLT, phenotypic score 1 or 2); null variants (“WASP absent”) are associated with severe disease (WAS, phenotypic score 3-5) (PMID: 12969986).

Although most female carriers are asymptomatic, there are rare reports of carrier females that are affected due to skewed X-inactivation (GeneReviews, OMIM, PMID: 23689198).

Created: 6 Feb 2025, 5:29 a.m. | Last Modified: 6 Feb 2025, 5:29 a.m.

Panel Version: 1.1459

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neutropenia, severe congenital, X-linked, MIM#300299; Thrombocytopenia, X-linked, MIM#313900; Wiskott-Aldrich syndrome, MIM#301000

Publications

• 12969986
• 23689198
• 20301357
• 34307257