Novel Nonsense Mutation in SMARCD2 Gene Results in Dysplasia of All Myeloid Cell Lines

ABSTRACT

Specific granule deficiency type II (SGD2) is a rare heterogeneous congenital disease characterized by early-onset life-threatening infections. SGD2 is caused by autosomal recessive mutations in the SMARCD2 gene.Prenatal screening in our patient revealed a novel homozygous nonsense mutation in SMARCD2 (c.208C>T, p.Gln70*).Postnatally, she suffered from infections, pneumonia, cholestasis, mucocutaneous bleeding, and dysmorphic features, including clubfoot. Hematological findings included neutropenia, monocytosis, myelodysplasia, and thrombocytopenia. In contrast to previous cases, this patient presented with dysplasia of all myeloid lineages, including hypogranular neutrophils, pseudo Pelger-Huët, macrothrombocytes, bilobular monocytes, and dysplastic erythroblasts. Due to the severity of her condition, she passed away after 1.5 months.This report illustrates the role of SMARCD2 in hematopoiesis and provides an overview of all previously described SGD2 patients.The authors have confirmed clinical trial registration is not needed for this submission.