The PIEZO1 gene mutation (c.2005G>T) causes iron overload cardiomyopathy: a case report

Supplemental Digital Content is available in the text Abstract Background: Cardiomyopathy has a variety of etiologies. Here, we report a case of iron overload cardiomyopathy (IOC) in combination with hereditary stomatocytosis (HST) due to a rare mutation in the PIEZO1 gene. Case summary: A 31-year-old man presented to the clinic with a new onset of fatigue and abdominal distension. He had a history of 9-year cholelithiasis, 4-year hemolytic anemia, 7-month diabetes mellitus (DM), and 6-month low sex drive. The specific features of bronze skin, liver palms, yellow eyes, DM, and cardiomyopathy raised our suspicion of hemochromatosis, which was confirmed by an elevated serum ferritin concentration and high transferrin saturation. Echocardiography and cardiovascular magnetic resonance (CMR) imaging demonstrated dilation of all cardiac cavities with a left ventricular ejection fraction of 30%. CMR T2∗ mapping showed myocardial, hepatic, and pancreatic siderosis. Next-generation sequencing identified one missense variant in the PIEZO1 gene (c.2005G>T), which conferred HST and hyperferritinemia. We screened his close family members and identified his son as a heterozygous carrier of this variant, who had intermittent jaundice. Conclusion: In this case, the PIEZO1 c.2005G>T mutation conferred HST and IOC, complicated with cholelithiasis, DM, and low sex drive. Bronze skin, liver cirrhosis, cardiomyopathy, and DM are red flags, while magnetic resonance imaging T2∗ mapping, blood iron metabolism markers, and gene testing are valuable in the diagnosis.