In:
Blood Advances, American Society of Hematology, Vol. 6, No. 18 ( 2022-09-27), p. 5279-5284
Abstract:
While loss-of-function variants in the WAS gene are associated with Wiskott-Aldrich syndrome and lead to microthrombocytopenia, gain-of-function variants of WAS are associated with X-linked neutropenia (XLN) and the absence of microthrombocytopenia. Only a few XLN families have been reported so far, and their platelet phenotype was not described in detail. To date, no renal involvement was described in XLN. In the present study, we report exome sequencing of individuals from 3 generations of a family with a dominant disease combining neutropenia, macrothrombocytopenia, and renal failure. We identified a heterozygous missense gain-of-function variant in the WAS gene (c.881T & gt;C, p.I294T) that segregates with the disease and is already known to cause XLN. There was no pathogenic variant in MYH9, TUBB1, or ACTN1. This is the first report of a WAS gain-of-function variant associated with both the hematological phenotype of XLN (neutropenia, macrothrombocytopenia) and renal disease (proteinuria, renal failure) with glomerular tip lesion hyalinosis and actin condensations in effaced podocytes foot processes.
Type of Medium:
Online Resource
ISSN:
2473-9529
,
2473-9537
DOI:
10.1182/bloodadvances.2021006789
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2022
detail.hit.zdb_id:
2876449-3
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