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. 2023 Dec;70(12):e30671.
doi: 10.1002/pbc.30671. Epub 2023 Sep 15.

Clinical and transcriptomic characteristics of a novel SMARCD2 mutation that disrupts neutrophil maturation and function

Laura Dotta  1 , Giulia Baresi  2 , Nicola Tamassia  3 , Federica Calzetti  3 , Francisco Bianchetto-Aguilera  3 , Sara Gasperini  3 , Elisa Gardiman  3 , Marco Chiarini  4 , Daniele Moratto  4 , Giovanni Martellosio  5 , Federico Serana  5 , Moira Micheletti  5 , Daniela Tregambe  5 , Vincenzo Pintabona  2 , Elena Soncini  2 , Antonella Meini  6 , Maria Federica Girelli  6 , Alessandra Beghin  7 , Arnalda Lanfranchi  7 , Mattia Bugatti  8 , Duilio Brugnoni  9 , Annarosa Soresina  6 , Alessandro Plebani  1 , Marco Cassatella  3 , William Vermi  8 , Fulvio Porta  2 , Raffaele Badolato  1
Affiliations

Clinical and transcriptomic characteristics of a novel SMARCD2 mutation that disrupts neutrophil maturation and function

Laura Dotta et al. Pediatr Blood Cancer. 2023 Dec.

Abstract

We report a novel case of SMARCD2 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily D, member 2) mutation successfully treated with hematopoietic stem cell transplantation. The female patient presented delayed cord separation, chronic diarrhea, skin abscesses, skeletal dysmorphisms, and neutropenia with specific granule deficiency. Analysis of the transcriptomic profile of peripheral blood sorted mature and immature SMARCD2 neutrophils showed defective maturation process that associated with altered expression of genes related to specific, azurophilic, and gelatinase granules, such as LTF, CRISP3, PTX3, and CHI3L1. These abnormalities account for the prevalence of immature neutrophils in the peripheral blood, impaired function, and deregulated inflammatory responses.

Keywords: SMARCD2; inborn errors of immunity; neutrophils.

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References

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