PIEZO1 Hypomorphic Variants in Congenital Lymphatic Dysplasia Cause Shape and Hydration Alterations of Red Blood Cells
| Autor: | Immacolata Andolfo, Gianluca De Rosa, Edoardo Errichiello, Francesco Manna, Barbara Eleni Rosato, Antonella Gambale, Annalisa Vetro, Valeria Calcaterra, Gloria Pelizzo, Lucia De Franceschi, Orsetta Zuffardi, Roberta Russo, Achille Iolascon |
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| Přispěvatelé: | Andolfo, Immacolata, De Rosa, Gianluca, Errichiello, Edoardo, Manna, Francesco, Rosato, Barbara Eleni, Gambale, Antonella, Vetro, Annalisa, Calcaterra, Valeria, Pelizzo, Gloria, De Franceschi, Lucia, Zuffardi, Orsetta, Russo, Roberta, Iolascon, Achille |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Physiology Spherocytosis spherocytosis Case Report Biology spherocytosi Compound heterozygosity lcsh:Physiology Hereditary spherocytosis 03 medical and health sciences 0302 clinical medicine Physiology (medical) medicine red blood cell alterations lcsh:QP1-981 Overhydrated hereditary stomatocytosis overhydration red blood cell alteration lymphedema medicine.disease 030104 developmental biology Lymphatic system Dysplasia stomatocytosis Dehydrated hereditary stomatocytosis PIEZO1 PIEZO1 lymphedema red blood cell alterations overhydration stomatocytosis spherocytosis Stomatocytosis 030215 immunology |
| Zdroj: | Frontiers in Physiology Frontiers in Physiology, Vol 10 (2019) |
| ISSN: | 1664-042X |
| Popis: | PIEZO1 is a cation channel activated by mechanical force. It plays an important physiological role in several biological processes such as cardiovascular, renal, endothelial and hematopoietic systems. Two different diseases are associated with alteration in the DNA sequence of PIEZO1: (i) dehydrated hereditary stomatocytosis (DHS1, #194380), an autosomal dominant hemolytic anemia caused by gain-of-function mutations; (ii) lymphatic dysplasia with non-immune fetal hydrops (LMPH3, #616843), an autosomal recessive condition caused by biallelic loss-of-function mutations. We analyzed a 14-year-old boy affected by severe lymphatic dysplasia already present prenatally, with peripheral edema, hydrocele, and chylothoraces. By whole exome sequencing, we identified compound heterozygosity for PIEZO1, with one splicing and one deletion mutation, the latter causing the formation of a premature stop codon that leads to mRNA decay. The functional analysis of the erythrocytes of the patient highlighted altered hydration with the intracellular loss of the potassium content and structural abnormalities with anisopoikolocytosis and presence of both spherocytes and stomatocytes. This novel erythrocyte trait, sharing features with both hereditary spherocytosis and overhydrated hereditary stomatocytosis, complements the clinical features associated with loss-of-function mutations of PIEZO1 in the context of the generalized lymphatic dysplasia of LMPH3 type. |
| Databáze: | OpenAIRE |
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