# Novel compound heterozygous PIEZO1 variants in dehydrated hereditary stomatocytosis initially suspected as myelodysplastic syndromes: a case report

## TL;DR

A rare blood disorder was misdiagnosed as a bone marrow disease but correctly identified through genetic testing, leading to successful treatment.

## Contribution

Identification of novel compound heterozygous PIEZO1 variants in a DHS case initially suspected as MDS.

## Key findings

- Compound heterozygous PIEZO1 variants c.6622A>G and c.3160C>A were found to cause DHS.
- Allogeneic hematopoietic stem cell transplantation resolved hematological abnormalities in the patient.
- Genetic testing confirmed DHS diagnosis after years of misdiagnosis as MDS.

## Abstract

Dehydrated hereditary stomatocytosis (DHS) is a rare autosomal dominant congenital non-immune hemolytic anemia caused by pathogenic variants in the PIEZO1 gene. Its clinical presentation often overlaps with other hematological disorders, leading to diagnostic challenges and potential mismanagement.

A 22-year-old man presented with a 7-year history of anemia initially misdiagnosed as myelodysplastic syndrome (MDS) due to hypercellular bone marrow findings and MDS-like features. Over time, his condition progressed to include cerebral venous sinus thrombosis (CVST), a severe complication. Comprehensive genetic testing at our hospital using whole-exome sequencing (WES) revealed novel compound heterozygous PIEZO1 variants: NM_001142864.4: c.6622A>G (p.Ile2208Val) and NM_001142864.4: c.3160C>A (p.Leu1054Met). These findings confirmed the diagnosis of DHS. The patient underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), resulting in resolution of his hematological abnormalities and symptoms.

This case underscores the importance of considering DHS in patients with unexplained anemia and MDS-like features, particularly when associated with thrombotic complications. It highlights the critical role of genetic testing in diagnosing rare hereditary anemias and demonstrates that allo-HSCT can be a curative treatment in selected cases.