Novel Frameshift Autosomal Recessive Loss-of-Function Mutation in SMARCD2 Encoding a Chromatin Remodeling Factor Mediate
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ORIGINAL ARTICLE
Novel Frameshift Autosomal Recessive Loss-of-Function Mutation in SMARCD2 Encoding a Chromatin Remodeling Factor Mediates Granulopoiesis Esra Yucel 1 & Ibrahim Serhat Karakus 2,3 & Ana Krolo 4,5,6 & Ayca Kiykim 7 & Raul Jimenez Heredia 4,5,6,8 & Zeynep Tamay 1 & Funda Erol Cipe 9 & Elif Karakoc-Aydiner 2,3 & Ahmet Ozen 2,3 & Serap Karaman 10 & Kaan Boztug 4,5,6,8,11 & Safa Baris 2,3 Received: 23 May 2020 / Accepted: 28 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose Recently, a new form of congenital neutropenia that is caused by germline biallelic loss-of-function mutations in the SMARCD2 gene was described in four patients. Given the rarity of the condition, the clinical spectrum of the disease has remained elusive. We here report a new patient with a novel frameshift mutation and compare our patient with the previously reported SMARCD2-mutant patients, aiming to provide a more comprehensive understanding of the natural course of the disease. Methods Clinical and laboratory findings of all reported patients were reviewed. Next-generation sequencing was performed to identify the causative genetic defect. Data on the hematopoietic stem cell transplantation including stem cell sources, conditioning regimen, engraftment, graft-versus-host disease, and infections were also collected. Results An 11-year-old female patient had a variety of infections including sepsis, deep tissue abscesses, otitis, pneumonia, gingivitis, and diarrhea since infancy. A novel homozygous mutation in SMARCD2 (c.93delG, p.Ala32Argfs*80) was detected. Bone marrow examination showed hypocellularity and decreased neutrophils with diminished granules and myeloid dysplasia, but no blast excess as in previously reported patients. The neutropenia was non-responsive even to higher doses of granulocyte colony-stimulating factor (G-CSF); therefore, the patient was transplanted at 10 years of age from a HLA-A allele–mismatched unrelated donor using a reduced toxicity conditioning regimen and recovered successfully. Compared with the previous four cases, our patient showed longer survival before transplantation without blastic transformation. Conclusion Distinctive myeloid features and long-term follow-up including therapy options are presented for the newly described case of SMARCD2 deficiency. This disorder is apparent at infancy and requires early transplantation due to the unrelenting disease course despite conventional therapy. Esra Yucel and Ibrahim Serhat Karakus contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10875-020-00878-4) contains supplementary material, which is available to authorized users. * Safa Baris [email protected]
6
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
7
Faculty of Medicine, Division of Pediatric Allergy and Immunology, Istanbul Cerrahpasa University, Istanbul, Turkey
1
Istanbul Faculty of Medicine, Division of
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