Combined Immunodeficiency

Gene: WAS

Green List (high evidence)

Neutropenia, severe congenital, X-linked
17 males from 4 unrelated families; gain of function; multiple mouse models
Missense variants were identified in all individuals (I294T, S272P & L270P) resulting in gain-of-function of actin regulator.
Individuals typically presented with chronic neutropaenia, monocytopaenia, recurrent bacterial infections, and reduced NK cells and lymphocyte proliferation.
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Wiskott-Aldrich syndrome
Over 20 unrelated individuals; loss of function; multiple mouse models, and Zebrafish models
Individuals showed deletion & missense variants in the PH domain and at CpG dinucleotide sites.
They are characterised by a triad of thrombocytopenia, eczema and immune deficiency. Recurrent infections, bloody diarrhoea and other hemorrhagic manifestations are usually the first signs of presentation.
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Thrombocytopenia, X-linked
8 individuals from 6 unrelated families; loss of function; mouse models
Identified missense, small deletions and insertions, and splice site variants in these individuals, resulting in eliminating a restriction enzyme site in the normal sequence or premature termination.
Individuals are typically characterised by isolated thrombocytopenia with small-sized platelets and high IgA or IgE serum levels.
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Green- Neutropenia, severe congenital, X-linked (GoF)
Green- Wiskott-Aldrich syndrome (LoF)
Green-Thrombocytopenia, X-linked (LoF)

Created: 26 Aug 2021, 4:25 a.m. | Last Modified: 26 Aug 2021, 4:25 a.m.

Panel Version: 0.381

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

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

Publications

• 11242115
• 19006568
• 16804117
• 8069912
• 10575547
• 7579329
• 7795648
• 23807894

Mode of pathogenicity
Other

Green List (high evidence)

Elevated IgE reported.

Created: 25 Aug 2021, 12:20 a.m. | Last Modified: 25 Aug 2021, 12:20 a.m.

Panel Version: 0.36

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

Phenotypes
Thrombocytopenia, X-linked, MIM# 313900

Publications

• 34390440