Clinical and biological features in PIEZO1-hereditary xerocytosis and Gardos-channelopathy: A retrospective series of 126 patients.

Fiche publication

Date publication

janvier 2019

Journal

Haematologica

Auteurs

Membres identifiés du Cancéropôle Est :
Pr DECONINCK Eric

Tous les auteurs :
Picard V, Guitton C, Thuret I, Rose C, Bendelac L, Ghazal K, Aguilar-Martinez P, Badens C, Barro C, Bénéteau C, Berger C, Cathébras P, Deconinck E, Delaunay J, Durand JM, Firah N, Galactéros F, Godeau B, Jaïs X, de Jaureguiberry JP, Le Stradic C, Lifermann F, Maffre R, Morin G, Perrin J, Proulle V, Ruivard M, Toutain F, Lahary A, Garçon L

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/30655378

Résumé

We describe clinical, hematological and genetic characteristics of a retrospective series of 126 subjects from 64 families with hereditary xerocytosis. Twelve patients from 6 families carried a KCNN4 mutation, 5 recurrent p.Arg352His mutations and one new deletion at the exon 7-intron 7 junction. Forty-nine families carried a PIEZO1 mutation, including known recurrent mutations in only one third of the cases and private sequence variations in others; 12 new probably pathogenic missense mutations were identified. The two dominant features leading to diagnosis were hemolysis that persisted after splenectomy and hyperferritinemia, with an inconstant correlation to liver iron content assessed by magnetic resonance imaging. PIEZO1-hereditary xerocytosis was characterized by compensated hemolysis in most cases, perinatal edema of heterogeneous severity in more than 20% of families and a major risk of post-splenectomy thrombotic events, including a high frequency of portal thrombosis. In KCNN4-related disease, the main symptoms were more severe anemia, hemolysis and iron overload, with no clear sign of red cell dehydration; therefore, this disorder would be better described as a Gardos channelopathy. These data on the largest series to date indicated that PIEZO1-hereditary xerocytosis and Gardos channelopathy are not the same disease although they share hemolysis, a high rate of iron overload and inefficient splenectomy. They demonstrate the high variability in clinical expression as well as genetic bases of PIEZO1-hereditary xerocytosis. These results will help to improve the diagnosis of hereditary xerocytosis and to provide recommendations on the clinical management in terms of splenectomy, iron overload and pregnancy follow-up.