DNAJC21-related thrombocytopenia in a young adult female

Area of Science:

• Genetics and Molecular Biology
• Hematology
• Rare Diseases

Background:

• Inherited bone marrow failure syndromes (IBMFS) encompass a group of rare genetic disorders.
• Bone marrow failure type 3 (BMFS3), characterized by mutations in DNAJC21, is a rare subtype of IBMFS.
• Previously, 19 pediatric cases of BMFS3 have been documented, with limited understanding of its adult clinical manifestations.

Observation:

• A 20-year-old female presented with persistent thrombocytopenia, dysmorphic features, and ovarian agenesis.
• Genetic analysis revealed a novel frameshift variant in the DNAJC21 gene, confirming a diagnosis of BMFS3.
• This case represents the first reported adult patient with BMFS3.

Findings:

• The adult patient's presentation indicates a milder clinical spectrum for DNAJC21-related disorders than previously recognized.
• The findings suggest that BMFS3 can manifest with less severe symptoms in adulthood, potentially including non-progressive thrombocytopenia.
• This expands the genotypic and phenotypic spectrum of disorders associated with DNAJC21 variants.

Implications:

• Re-evaluation of undiagnosed patients with persistent thrombocytopenia, particularly adults, is warranted.
• Offering whole exome sequencing (WES) to a broader patient population can aid in diagnosing rare genetic conditions like BMFS3.
• Further investigation into DNAJC21 variants will enhance understanding of BMFS3 pathophysiology and improve diagnostic strategies.