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

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

doi:10.1002/pbc.30671

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

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

Authors

Laura Dotta¹, Giulia Baresi², Nicola Tamassia³, Federica Calzetti³, Francisco Bianchetto-Aguilera³, Sara Gasperini³, Elisa Gardiman³, Marco Chiarini⁴, Daniele Moratto⁴, Giovanni Martellosio⁵, Federico Serana⁵, Moira Micheletti⁵, Daniela Tregambe⁵, Vincenzo Pintabona², Elena Soncini², Antonella Meini⁶, Maria Federica Girelli⁶, Alessandra Beghin⁷, Arnalda Lanfranchi⁷, Mattia Bugatti⁸, Duilio Brugnoni⁹, Annarosa Soresina⁶, Alessandro Plebani¹, Marco Cassatella³, William Vermi⁸, Fulvio Porta², Raffaele Badolato¹

Affiliations

¹ Department of Pediatrics, ASST Spedali Civili of Brescia, Department of Clinical and Experimental Sciencies, University of Brescia, Brescia, Italy.
² Pediatric Oncohaematology and BMT Unit, ASST Spedali Civili of Brescia, Brescia, Italy.
³ General Pathology Section, Department of Medicine, University of Verona, Verona, Italy.
⁴ Flow Cytometry Unit, Clinical Chemistry Laboratory, ASST Spedali Civili of Brescia, Brescia, Italy.
⁵ Hematology Unit, Clinical Chemistry Laboratory, Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy.
⁶ Department of Pediatrics, ASST Spedali Civili of Brescia, Brescia, Italy.
⁷ Stem Cell Laboratory, Section of Hematology and Blood Coagulation, Clinical Chemistry Laboratory, Diagnostics Department, ASST Spedali Civili of Brescia, Brescia, Italy.
⁸ Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
⁹ Department of Laboratory Diagnostics, ASST Spedali Civili of Brescia, Brescia, Italy.

PMID: 37712719
DOI: 10.1002/pbc.30671

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.