Clinical and genetic spectrum of SBDS and DNAJC21 gene variants in bone marrow failure cases: Atypical and cryptic presentations

Abstract

Shwachman-Diamond syndrome (SDS) is a rare bone marrow failure disorder presenting with early onset cytopenia, chronic diarrhea, and failure to thrive with biallelic pathogenic variants in the SBDS (SDS1; 260400) gene. Recently, biallelic variants in DNAJC21 (BMFS3; 617052) and ELF1 genes have also been shown to be related to SDS-like phenotype. Additionally, a monoallelic variant of the SBDS gene has been linked to the development of idiopathic aplastic anemia (IAA). We screened 405 marrow failure cases and noted 10 different SDS gene variants in 3 % (11/405) cases, of which 2 (20 %) were novel; DNAJC21 variant c.98-2delA and SBDS variant c.359T>C. In this report, we highlight the detailed phenotype and genotype of these cases and emphasize cryptic and atypical presentations.