Novel mutations in the PIEZO1 gene in hereditary stomatocytosis: a severe case of anaemia and hepatosplenomegaly

Dehydrating hereditary stomatocytosis (DHS) is a rare hereditary haemolytic anaemia inherited in an autosomal dominant pattern, characterised by macrocytosis, the presence of stomatocytes and erythrocyte dehydration. The disease is based on increased permeability of erythrocyte membranes due to certain genetic defects (missense mutations in the PIEZO1 and KCNN4 genes), which causes an imbalance in intracellular cation concentrations. The disease has variable clinical manifestations, which complicates its timely diagnosis. Aim - to describe a clinical case of DHS1 caused by two novel variants in the PIEZO1 gene c.5590C>T (p.Arg 1864Cys) and c.76C>T (p.Arg26Cys) in a 5-year-old girl with transfusion-dependent anaemia, massive hepatosplenomegaly and psychophysical developmental delay. Clinical case. The girl has been ill since birth. Increased abdominal size, hepatosplenomegaly and decreased blood counts were first noticed at the age of 7 months. Severe anaemia was controlled by haemotransfusions. The initial pathological bone marrows (ВМ) examination diagnosed reticulin myelofibrosis. Multidisciplinary genetic tests were performed. Carriers without clinical significance were found epidermolysis bullosa (COL7A1 gene) and nephronoptosis (NPHP1 gene). NGS (Next-Generation Sequencing), a panel of hereditary anaemias, identified mutations c.5590C>T (p.Arg 1864Cys) and c.76 C>T (p.Arg26Cys) in the PIEZO1 gene, in combination with clinical and laboratory changes was diagnosed DHS1. Conclusions. DHS1 in children is a rare disease that can have a severe clinical course and cause significant diagnostic difficulties. The presence of two mutation variants in the PIEZO1 gene: c.5590C>T (p.Arg1864Cys) and c.76C>T (p.Arg26Cys) can aggravate the disease. Visual assessment of blood smear and NGS are important methods for the diagnosis of hereditary anaemias. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.