A novel primary human immunodeficiency due to deficiency in the WASP-interacting protein WIP.
A female offspring of consanguineous parents, showed features of Wiskott-Aldrich syndrome (WAS), including recurrent infections, eczema, thrombocytopenia, defective T cell proliferation and chemotaxis, and impaired natural killer cell function. Cells from this patient had undetectable WAS protein (WASP), but normal WAS sequence and messenger RNA levels. WASP interacting protein (WIP), which stabilizes WASP, was also undetectable. A homozygous c.1301C>G stop codon mutation was found in the WIPF1 gene, which encodes WIP. Introduction of WIP into the patient's T cells restored WASP expression. These findings indicate that WIP deficiency should be suspected in patients with features of WAS in whom WAS sequence and mRNA levels are normal.
A. Nocivelli Institute for Molecular Medicine, Pediatric Clinic, University of Brescia, and Laboratory of Genetic Disease of Childhood, Spedali Civili, 25123 Brescia, Italy.
Gaetana
G
Lanzi
Daniele
D
Moratto
Donatella
D
Vairo
Stefania
S
Masneri
Ottavia
O
Delmonte
Tiziana
T
Paganini
Silvia
S
Parolini
Giovanna
G
Tabellini
Cinzia
C
Mazza
Gianfranco
G
Savoldi
Davide
D
Montin
Silvana
S
Martino
Pierangelo
P
Tovo
Itai M
IM
Pessach
Michel J
MJ
Massaad
Narayanaswamy
N
Ramesh
Fulvio
F
Porta
Alessandro
A
Plebani
Luigi D
LD
Notarangelo
Raif S
RS
Geha
Silvia
S
Giliani
D001483:Base Sequence; D003598:Cytoskeletal Proteins / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D023061:Gene Order; D006801:Humans; D007231:Infant, Newborn; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D009154:Mutation; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics* / Q000276:immunology*; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics
D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; C109903:WIPF1 protein, human; D051316:Wiskott-Aldrich Syndrome Protein